Theodore Leng, MD, FACS

All Publications

• Impact of Anti-VEGF Treatment and Patient Characteristics on Vision Outcomes in Neovascular Age-related Macular Degeneration: Up to 6-Year Analysis of the AAO IRIS® Registry. Ophthalmology science Wykoff, C. C., Garmo, V., Tabano, D., Menezes, A., Kim, E., Fevrier, H. B., LaPrise, A., Leng, T. 2024; 4 (2): 100421

  Abstract

  To evaluate anti-VEGF treatment patterns and the influence of patient demographic and clinical characteristics on up to 6-year vision outcomes in neovascular age-related macular degeneration.Retrospective, multicenter, noninterventional registry study with up to 6 years of follow-up.A cohort of 254 655 eyes (226 767 patients) with first anti-VEGF injection and at least 2 years of follow-up; 160 423 eyes had visual acuity (VA) data.Anonymized patient data were collected in the United States through the IRIS® Registry (Intelligent Research in Sight).Changes in VA from baseline; frequency of and gaps between intravitreal anti-VEGF injections; treatment discontinuations; switching anti-VEGF agents; and influence of baseline clinical and demographic characteristics on VA.After a mean VA increase of 3.0 ETDRS letters at year 1, annual decreases led to a net loss from baseline of 4.6 letters after 6 years. Patients with longer follow-ups had better baseline and follow-up VA. From a mean of 7.2 in year 1 and 5.6 in year 2, mean injections plateaued between 4.2 to 4.6 in years 3 through 6. Treatment was discontinued in 38.8% of eyes and switched in 32.3%. When adjusting for differences at baseline, every additional injection resulted in a 0.68 letter improvement from baseline to year 1; thus, multiple injections in a year have the potential to be clinically meaningful. Older age, male gender, Medicaid insurance, and not being treated by a retina specialist were associated with a higher likelihood of vision loss at year 1. Of the patients, 58.5% lost ≥ 10 letters VA at least once during follow-up, with 14.5% of patients experiencing sustained poor vision after a median of 3.4 years.After modest mean VA improvement with intravitreal anti-VEGF injections at year 1, patients netted a loss of VA by year 6. Injection frequency decreased over time, and this was paired with a relatively high rate of discontinuation. Modeling suggested that more frequent injections were associated with better VA. Difficulty with continuous adherence to frequent intravitreal injections may have contributed to undertreatment resulting in less-than-optimal vision outcomes.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

  View details for DOI 10.1016/j.xops.2023.100421

  View details for PubMedID 38187126

  View details for PubMedCentralID PMC10767511

• Editorial: Generalizable and explainable artificial intelligence methods for retinal disease analysis: challenges and future trends. Frontiers in medicine Chen, Q., Leng, T., Niu, S., Trucco, E. 2024; 11: 1465369

  View details for DOI 10.3389/fmed.2024.1465369

  View details for PubMedID 39144659

  View details for PubMedCentralID PMC11322678

• Long-term Treatment Patterns for Diabetic Macular Edema: Up to 6-Year Follow-Up in the IRIS® Registry. Ophthalmology. Retina Kuo, B. L., Tabano, D., Garmo, V., Kim, E., Leng, T., Hatfield, M., LaPrise, A., Singh, R. P. 2024

  Abstract

  To characterize anti-vascular endothelial growth factor (VEGF) intravitreal therapy (IVT) patterns and long-term visual outcomes among patients with diabetic macular edema (DME) in routine clinical practice in the United States.Retrospective analysis of the American Academy of Ophthalmology's Intelligent Research in Sight (IRIS®) Registry.; Participants: Treatment-naïve patients with DME (no previous IVT in the past 12 months) initiating anti-VEGF IVT from 1/1/2015-3/31/2021.Baseline characteristics, treatment patterns, and long-term visual acuity (VA) outcomes were reported for up to 6 years of follow-up.Outcomes included the annualized number of injections, change in VA, and anti-VEGF agents.A total of 190,345 eyes met inclusion criteria. After 1 year of anti-VEGF IVT initiation, eyes received a mean of 3.9 (±2.8) injections and gained +3.2 (±16.4) letters of vision. Of the 1,236 eyes with year 6 data, eyes received a mean of 2.9 (±2.1) injections in year 6 and gained +0.5 (±19.7) letters from baseline. The number of injections decreased, and injection intervals increased year over year up to 6 years regardless of baseline VA initiation. The average injection interval was 10-weeks in year 1, then widened to 13.2 in year 2, before plateauing in years 3-6 (12.6, 12.3, 12.2, and 12.3 weeks respectively). Improvements in VA from baseline were greatest in eyes that received 5 or more injections each year. At the end of follow-up, eyes with good baseline vision (> 20/25) lost vision, whereas those with worse baseline vision (< 20/25) gained vision. Although 51.7% of patients with DME discontinued IVT after a mean of 6 months, 32.8% re-initiated anti-VEGF IVT. Worse VA outcomes were associated with patients of Hispanic ethnicity (-1.08 [-1.34, -0.83] compared to non-Hispanic), Medicaid insurance (-1.15 [-1.48, -0.81] compared to Commercial), and older age (-0.06 [-0.07, -0.05] each additional year) CONCLUSIONS: Patients with DME in the routine clinical settings receive fewer injections than those in clinical trials and fewer than recommended per the label of FDA approved anti-VEGF IVT.

  View details for DOI 10.1016/j.oret.2024.05.017

  View details for PubMedID 38830485

• EYE-Llama, an in-domain large language model for ophthalmology. bioRxiv : the preprint server for biology Haghighi, T., Gholami, S., Sokol, J. T., Kishnani, E., Ahsaniyan, A., Rahmanian, H., Hedayati, F., Leng, T., Alam, M. N. 2024

  Abstract

  Background: Training Large Language Models (LLMs) with in-domain data can significantly enhance their performance, leading to more accurate and reliable question-answering (QA) systems essential for supporting clinical decision-making and educating patients.Methods: This study introduces LLMs trained on in-domain, well-curated ophthalmic datasets. We also present an open-source substantial ophthalmic language dataset for model training. Our LLMs (EYE-Llama), first pre-trained on an ophthalmology-specific dataset, including paper abstracts, textbooks, EyeWiki, and Wikipedia articles. Subsequently, the models underwent fine-tuning using a diverse range of QA datasets. The LLMs at each stage were then compared to baseline Llama 2, ChatDoctor, and ChatGPT (GPT3.5) models, using four distinct test sets, and evaluated quantitatively (Accuracy, F1 score, and BERTScore) and qualitatively by two ophthalmologists.Results: Upon evaluating the models using the American Academy of Ophthalmology (AAO) test set and BERTScore as the metric, our models surpassed both Llama 2 and ChatDoctor in terms of F1 score and performed equally to ChatGPT, which was trained with 175 billion parameters (EYE-Llama: 0.57, Llama 2: 0.56, ChatDoctor: 0.56, and ChatGPT: 0.57). When evaluated on the MedMCQA test set, the fine-tuned models demonstrated a higher accuracy compared to the Llama 2 and ChatDoctor models (EYE-Llama: 0.39, Llama 2: 0.33, ChatDoctor: 0.29). However, ChatGPT outperformed EYE-Llama with an accuracy of 0.55. When tested with the PubmedQA set, the fine-tuned model showed improvement in accuracy over both the Llama 2, ChatGPT, and ChatDoctor models (EYE-Llama: 0.96, Llama 2: 0.90, ChatGPT: 0.93, ChatDoctor: 0.92).Conclusion: The study shows that pre-training and fine-tuning LLMs like EYE-Llama enhances their performance in specific medical domains. Our EYE-Llama models surpass baseline Llama 2 in all evaluations, highlighting the effectiveness of specialized LLMs in medical QA systems. (Funded by NEI R15EY035804 (MNA) and UNC Charlotte Faculty Research Grant (MNA).).

  View details for DOI 10.1101/2024.04.26.591355

  View details for PubMedID 38746183

• Mirrored X-Net: Joint classification and contrastive learning for weakly supervised GA segmentation in SD-OCT PATTERN RECOGNITION Ji, Z., Ma, X., Leng, T., Rubin, D. L., Chen, Q. 2024; 153

  View details for DOI 10.1016/j.patcog.2024.110507

  View details for Web of Science ID 001217874300001

• Comparison of Methods of Clinical Trial Emulation Utilizing Data From the Comparison of AMD Treatment Trial (CATT) and the IRIS® Registry. Ophthalmology science Fevrier, H., LaPrise, A., Mbagwu, M., Leng, T., Torres, A. Z., Borkar, D. S. 2024; 4 (5): 100524

  Abstract

  We used exact matching and inverse propensity score weighting (IPSW) using real-world data (RWD) from the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) to emulate the 2 pro re nata (prn) treatment arms from the Comparison of AMD Treatment Trial (CATT) and to compare the outcomes of the RWD arms to the 2 monthly treatment arms from the clinical trial.Retrospective cohort study utilizing deidentified electronic health record registry data and patient-level deidentified clinical trial data.All treatment-naive patient eyes with neovascular age-related macular degeneration treated with ranibizumab or bevacizumab only for 1 year from either the CATT or the IRIS Registry.Patients were identified in the IRIS Registry between October 1, 2015 and December 31, 2019. After all nonimaging-based inclusion and exclusion criteria from the CATT were applied, patient eyes receiving bevacizumab or ranibizumab only on a prn basis were identified as the eligible cohort. Exact matching and ISPW was applied based on age, gender, and baseline visual acuity.Mean change in visual acuity, in approximated ETDRS letters, between baseline and 1 year for the IRIS Registry prn treatment arms generated by exact matching and IPSW.We identified 427 eyes treated with ranibizumab prn and 771 eyes treated with bevacizumab prn. Using exact matching, 98% (n = 281) of CATT patient eyes in the bevacizumab monthly treatment arm and 87% (n = 261) of CATT patient eyes in the ranibizumab monthly treatment arm were matched to a patient eye in the IRIS Registry. For the ranibizumab prn treatment arm, patient eyes generated using exact matching gained 1.9 letters and those generated using IPSW gained 2.8 letters (exact matching: 1.9 letters ± 14.0 vs. IPSW: 2.8 letters ± 15.0 letters, P = 0.43). For the bevacizumab prn treatment arm, patient eyes generated using exact matching gained 2.4 letters and those generated using IPSW gained 2.1 letters (exact matching: 2.4 letters ± 15.4 vs. IPSW: 2.1 letters ± 16.0 letters, P = 0.79).Both exact matching and IPSW produced similar results in emulating the prn treatment arms of the CATT using IRIS Registry data and patient-level clinical trial data. Similar to prior real-world studies, the clinical outcomes were significantly worse in the IRIS Registry treatment arms compared with the clinical trial.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

  View details for DOI 10.1016/j.xops.2024.100524

  View details for PubMedID 38881608

  View details for PubMedCentralID PMC11179401

• Feasibility of cross-vendor linkage of ophthalmic images with electronic health record data: an analysis from the IRIS Registry®. JAMIA open Mbagwu, M., Chu, Z., Borkar, D., Koshta, A., Shah, N., Torres, A., Kalvaria, H., Lum, F., Leng, T. 2024; 7 (1): ooae005

  Abstract

  To link compliant, universal Digital Imaging and Communications in Medicine (DICOM) ophthalmic imaging data at the individual patient level with the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight).A retrospective study using de-identified EHR registry data.IRIS Registry records.DICOM files of several imaging modalities were acquired from two large retina ophthalmology practices. Metadata tags were extracted and harmonized to facilitate linkage to the IRIS Registry using a proprietary, heuristic patient-matching algorithm, adhering to HITRUST guidelines. Linked patients and images were assessed by image type and clinical diagnosis. Reasons for failed linkage were assessed by examining patients' records.Success rate of linking clinicoimaging and EHR data at the patient level.A total of 2 287 839 DICOM files from 54 896 unique patients were available. Of these, 1 937 864 images from 46 196 unique patients were successfully linked to existing patients in the registry. After removing records with abnormal patient names and invalid birthdates, the success linkage rate was 93.3% for images. 88.2% of all patients at the participating practices were linked to at least one image.Using identifiers from DICOM metadata, we created an automated pipeline to connect longitudinal real-world clinical data comprehensively and accurately to various imaging modalities from multiple manufacturers at the patient and visit levels. The process has produced an enriched and multimodal IRIS Registry, bridging the gap between basic research and clinical care by enabling future applications in artificial intelligence algorithmic development requiring large linked clinicoimaging datasets.

  View details for DOI 10.1093/jamiaopen/ooae005

  View details for PubMedID 38283883

  View details for PubMedCentralID PMC10811449

• Quantitative Characterization of Retinal Features in Translated OCTA. medRxiv : the preprint server for health sciences Badhon, R. H., Thompson, A. C., Lim, J. I., Leng, T., Alam, M. N. 2024

  Abstract

  Purpose: This study explores the feasibility of using generative machine learning (ML) to translate Optical Coherence Tomography (OCT) images into Optical Coherence Tomography Angiography (OCTA) images, potentially bypassing the need for specialized OCTA hardware.Methods: The method involved a generative adversarial network framework that includes a 2D vascular segmentation model and a 2D OCTA image translation model. This framework is designed to enhance the accuracy, resolution, and continuity of vascular regions in the translated OCTA (TR-\OCTA) images. The study utilizes a public dataset of 500 patients, divided into subsets based on resolution and disease status, to validate the quality of TR-OCTA images. The validation employs several quality and quantitative metrics to compare the translated images with ground truth OCTAs (GT-OCTA).Result: TR-OCTAs showed high image quality in both 3 and 6 mm datasets (high-resolution, moderate structural similarity and contrast quality compared to GT-OCTAs). There were slight discrepancies in vascular metrics, especially in diseased patients. Blood vessel features like tortuosity and vessel perimeter index showed better trend compared to density feature which is affected by local vascular distortions.Conclusion: This study presents a promising solution to the limitations of OCTA adoption in clinical practice by using ML to translate OCT data into OCTA images.Translation relevance: This study has the potential to significantly enhance the diagnostic process for retinal diseases by making detailed vascular imaging more widely available and reducing dependency on costly OCTA equipment.

  View details for DOI 10.1101/2024.02.23.24303275

  View details for PubMedID 38464168

• Acute Subretinal Fluid Accumulation Induced by Futibatinib Therapy for Malignant Metastatic Breast Cancer OPHTHALMIC SURGERY LASERS & IMAGING RETINA Chhoy, B., Wai, K. M., Leng, T. 2024; 55 (2): 109-111

  Abstract

  Alport syndrome is characterized by type IV collagen network disruptions leading to renal, auditory, and ocular manifestations. This case report details a 24-year-old man with Alport syndrome who developed a rhegmatogenous retinal detachment following macular hole repair. The patient underwent a successful vitrectomy and internal limiting membrane peel for macular hole repair but returned with vision loss due to retinal detachment five weeks later, which necessitated a combined scleral buckle and vitrectomy. This is the first case describing rhegmatogenous retinal detachment post-macular hole repair in Alport syndrome. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

  View details for DOI 10.3928/23258160-20231205-02

  View details for Web of Science ID 001178161800006

  View details for PubMedID 38408224

• AI-Human Hybrid Workflow Enhances Teleophthalmology for the Detection of Diabetic Retinopathy. Ophthalmology science Dow, E. R., Khan, N. C., Chen, K. M., Mishra, K., Perera, C., Narala, R., Basina, M., Dang, J., Kim, M., Levine, M., Phadke, A., Tan, M., Weng, K., Do, D. V., Moshfeghi, D. M., Mahajan, V. B., Mruthyunjaya, P., Leng, T., Myung, D. 2023; 3 (4): 100330

  Abstract

  Detection of diabetic retinopathy (DR) outside of specialized eye care settings is an important means of access to vision-preserving health maintenance. Remote interpretation of fundus photographs acquired in a primary care or other nonophthalmic setting in a store-and-forward manner is a predominant paradigm of teleophthalmology screening programs. Artificial intelligence (AI)-based image interpretation offers an alternative means of DR detection. IDx-DR (Digital Diagnostics Inc) is a Food and Drug Administration-authorized autonomous testing device for DR. We evaluated the diagnostic performance of IDx-DR compared with human-based teleophthalmology over 2 and a half years. Additionally, we evaluated an AI-human hybrid workflow that combines AI-system evaluation with human expert-based assessment for referable cases.Prospective cohort study and retrospective analysis.Diabetic patients ≥ 18 years old without a prior DR diagnosis or DR examination in the past year presenting for routine DR screening in a primary care clinic.Macula-centered and optic nerve-centered fundus photographs were evaluated by an AI algorithm followed by consensus-based overreading by retina specialists at the Stanford Ophthalmic Reading Center. Detection of more-than-mild diabetic retinopathy (MTMDR) was compared with in-person examination by a retina specialist.Sensitivity, specificity, accuracy, positive predictive value, and gradability achieved by the AI algorithm and retina specialists.The AI algorithm had higher sensitivity (95.5% sensitivity; 95% confidence interval [CI], 86.7%-100%) but lower specificity (60.3% specificity; 95% CI, 47.7%-72.9%) for detection of MTMDR compared with remote image interpretation by retina specialists (69.5% sensitivity; 95% CI, 50.7%-88.3%; 96.9% specificity; 95% CI, 93.5%-100%). Gradability of encounters was also lower for the AI algorithm (62.5%) compared with retina specialists (93.1%). A 2-step AI-human hybrid workflow in which the AI algorithm initially rendered an assessment followed by overread by a retina specialist of MTMDR-positive encounters resulted in a sensitivity of 95.5% (95% CI, 86.7%-100%) and a specificity of 98.2% (95% CI, 94.6%-100%). Similarly, a 2-step overread by retina specialists of AI-ungradable encounters improved gradability from 63.5% to 95.6% of encounters.Implementation of an AI-human hybrid teleophthalmology workflow may both decrease reliance on human specialist effort and improve diagnostic accuracy.Proprietary or commercial disclosure may be found after the references.

  View details for DOI 10.1016/j.xops.2023.100330

  View details for PubMedID 37449051

  View details for PubMedCentralID PMC10336195

• Progression of Geographic Atrophy: Retrospective Analysis of Patients from the IRIS® Registry (Intelligent Research in Sight). Ophthalmology science Rahimy, E., Khan, M. A., Ho, A. C., Hatfield, M., Nguyen, T. H., Jones, D., McKeown, A., Borkar, D., Leng, T., Ribeiro, R., Holekamp, N. 2023; 3 (4): 100318

  Abstract

  To evaluate disease progression and associated vision changes in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) in 1 eye and GA or neovascular AMD (nAMD) in the fellow eye using a large dataset from routine clinical practice.Retrospective analysis of clinical data over 24 months.A total of 256 635 patients with GA from the American Academy of Ophthalmology (Academy) IRIS® Registry (Intelligent Research in Sight) Registry (January 2016 to December 2017).Patients with ≥ 24 months of follow-up were grouped by fellow-eye status: Cohort 1, GA:GA; Cohort 2, GA:nAMD, each with (subfoveal) and without subfoveal (nonsubfoveal) involvement. Eyes with history of retinal disease other than AMD were excluded. Sensitivity analysis included patients who were managed by retina specialists and had a record of imaging within 30 days of diagnosis.Change in visual acuity (VA), occurrence of new-onset nAMD, and GA progression from nonsubfoveal to subfoveal.In total, 69 441 patients were included: 44 120 (64%) GA:GA and 25 321 (36%) GA:nAMD. Otherwise eligible patients (57 788) were excluded due to follow-up < 24 months. In both GA:GA and GA:nAMD cohorts, nonsubfoveal study eyes had better mean (standard deviation) VA at index (67 [19.3] and 66 [20.3] letters) than subfoveal eyes (59 [23.9] and 47 [26.9] letters), and 24-month mean VA changes were similar for nonsubfoveal (-7.6 and -6.2) and subfoveal (-7.9 and -6.5) subgroups. Progression to subfoveal GA occurred in 16.7% of nonsubfoveal study eyes in the GA:GA cohort and 12.5% in the GA:nAMD cohort. More new-onset study-eye nAMD was observed in the GA:nAMD (21.6%) versus GA:GA (8.2%) cohorts. Sensitivity analysis supported the robustness of the observations in the study.This retrospective analysis describes the natural progression of GA lesions and the decline in VA associated with the disease.Proprietary or commercial disclosure may be found after the references.

  View details for DOI 10.1016/j.xops.2023.100318

  View details for PubMedID 37274013

  View details for PubMedCentralID PMC10232896

• Artificial Intelligence Improves Patient Follow-Up in a Diabetic Retinopathy Screening Program. Clinical ophthalmology (Auckland, N.Z.) Dow, E. R., Chen, K. M., Zhao, C. S., Knapp, A. N., Phadke, A., Weng, K., Do, D. V., Mahajan, V. B., Mruthyunjaya, P., Leng, T., Myung, D. 2023; 17: 3323-3330

  Abstract

  We examine the rate of and reasons for follow-up in an Artificial Intelligence (AI)-based workflow for diabetic retinopathy (DR) screening relative to two human-based workflows.A DR screening program initiated September 2019 between one institution and its affiliated primary care and endocrinology clinics screened 2243 adult patients with type 1 or 2 diabetes without a diagnosis of DR in the previous year in the San Francisco Bay Area. For patients who screened positive for more-than-mild-DR (MTMDR), rates of follow-up were calculated under a store-and-forward human-based DR workflow ("Human Workflow"), an AI-based workflow involving IDx-DR ("AI Workflow"), and a two-step hybrid workflow ("AI-Human Hybrid Workflow"). The AI Workflow provided results within 48 hours, whereas the other workflows took up to 7 days. Patients were surveyed by phone about follow-up decisions.Under the AI Workflow, 279 patients screened positive for MTMDR. Of these, 69.2% followed up with an ophthalmologist within 90 days. Altogether 70.5% (N=48) of patients who followed up chose their location based on primary care referral. Among the subset of patients that were seen in person at the university eye institute under the Human Workflow and AI-Human Hybrid Workflow, 12.0% (N=14/117) and 11.7% (N=12/103) of patients with a referrable screening result followed up compared to 35.5% of patients under the AI Workflow (N=99/279; χ2df=2 = 36.70, p < 0.00000001).Ophthalmology follow-up after a positive DR screening result is approximately three-fold higher under the AI Workflow than either the Human Workflow or AI-Human Hybrid Workflow. Improved follow-up behavior may be due to the decreased time to screening result.

  View details for DOI 10.2147/OPTH.S422513

  View details for PubMedID 38026608

  View details for PubMedCentralID PMC10665027

• Vitreoretinal Specialist Use of Ancillary Testing: An IRIS® Registry Analysis. Clinical ophthalmology (Auckland, N.Z.) Vishwakarma, S., Borkar, D. S., LaPrise, A., Mbagwu, M., Leng, T. 2023; 17: 3077-3085

  Abstract

  To investigate patterns of ancillary imaging testing among vitreoretinal specialists for patients with vitreoretinal disease in the United States (US).Optical coherence tomography (OCT), color fundus photography (CFP), and fluorescein angiography (FA), ordered by vitreoretinal specialists and documented within the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) between 01 January 2018 and 31 December 2020, were retrospectively assessed. Trends in imaging modality choice were analyzed by payer type, geographic region, and practice type. Sub-analyses were conducted according to categorization of vitreoretinal specialists into those treating a high versus low volume of patients with neovascular age-related macular degeneration (nAMD).OCT was the most common imaging modality used, followed by CFP and FA. Following normalization, the highest volume of OCT procedures performed were identified among Medicare Advantage and Medicare Fee-for-Service beneficiaries, within the South of the US, and at medium and large practices. Minimal differences were observed for CFP and FA volume across payer types and regions. Across practice types, the largest volume of CFP and FA procedures were identified in small and private equity owned practices, respectively. Vitreoretinal specialists with a high nAMD volume more frequently performed OCT than those with a low nAMD volume.Vitreoretinal specialists demonstrated a strong preference for OCT, with real-world associations according to payer type, geographic location, and practice type. Volume of nAMD patients seen impacted the likelihood of specialists ordering OCTs.

  View details for DOI 10.2147/OPTH.S433338

  View details for PubMedID 37873056

  View details for PubMedCentralID PMC10590590

• Federated learning for diagnosis of age-related macular degeneration. Frontiers in medicine Gholami, S., Lim, J. I., Leng, T., Ong, S. S., Thompson, A. C., Alam, M. N. 2023; 10: 1259017

  Abstract

  This paper presents a federated learning (FL) approach to train deep learning models for classifying age-related macular degeneration (AMD) using optical coherence tomography image data. We employ the use of residual network and vision transformer encoders for the normal vs. AMD binary classification, integrating four unique domain adaptation techniques to address domain shift issues caused by heterogeneous data distribution in different institutions. Experimental results indicate that FL strategies can achieve competitive performance similar to centralized models even though each local model has access to a portion of the training data. Notably, the Adaptive Personalization FL strategy stood out in our FL evaluations, consistently delivering high performance across all tests due to its additional local model. Furthermore, the study provides valuable insights into the efficacy of simpler architectures in image classification tasks, particularly in scenarios where data privacy and decentralization are critical using both encoders. It suggests future exploration into deeper models and other FL strategies for a more nuanced understanding of these models' performance. Data and code are available at https://github.com/QIAIUNCC/FL_UNCC_QIAI.

  View details for DOI 10.3389/fmed.2023.1259017

  View details for PubMedID 37901412

  View details for PubMedCentralID PMC10613107

• Ophthalmology at the Forefront of Big Data Integration in Medicine: Insights from the IRIS Registry Database. The Yale journal of biology and medicine Knapp, A. N., Leng, T., Rahimy, E. 2023; 96 (3): 421-426

  Abstract

  Ophthalmology stands at the vanguard of incorporating big data into medicine, as exemplified by the integration of The Intelligent Research in Sight (IRIS) Registry. This synergy cultivates patient-centered care, demonstrates real world efficacy and safety data for new therapies, and facilitates comprehensive population health insights. By evaluating the creation and utilization of the world's largest specialty clinical data registry, we underscore the transformative capacity of data-driven medical paradigms, current shortcomings, and future directions. We aim to provide a scaffold for other specialties to adopt big data integration into medicine.

  View details for DOI 10.59249/VUPM2510

  View details for PubMedID 37780991

  View details for PubMedCentralID PMC10524808

• Quantification of retinal neuroprotection achieved by two different human neural stem cell formulations in the RCS rat Arrizabalaga, S., Uchida, N., Curtis, A., Navarro, I., Stoddard, J., Tsukamoto, A., Leng, T., Ryals, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053795603139

• Generalizability of Convolutional Neural Network and Vision Transformer-Based OCT Segmentation Models Pely, A., Wu, Z., Leng, T., Gao, S. S., Chen, H., Hejrati, M., Zhang, M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053758301001

• IMPUTATION OF DISEASE SEVERITY FOR DIABETIC RETINOPATHY CLINICAL ENCOUNTERS IN THE IRIS (R) REGISTRY (INTELLIGENT RESEARCH IN SIGHT) Chapman, R., Nguyen, T., Hatfield, M., Leng, T., Mbagwu, M., Torres, A., Borkar, D. ELSEVIER SCIENCE INC. 2023: S386

  View details for Web of Science ID 001031473302427

• Automated identification of geographic atrophy eyes with and without subfoveal involvement using machine learning and real-world ophthalmic images in the IRIS Registry Chu, Z., Leng, T., Borkar, D. S., Candano, C., Le, K., Ramakrishnan, A., Khapare, K., Mbagwu, M., Torres, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053758300340

• Real world outcomes from artificial intelligence to detect diabetic retinopathy in the primary care setting: 12 month experience Knapp, A. N., Dow, E., Chen, K., Khan, N. C., Do, D. V., Mahajan, V., Mruthyunjaya, P., Leng, T., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053758300331

• A federated learning framework for training multi-class OCT classification models Gholami, S., Leng, T., Alam, M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001052064700045

• Geographic atrophy diagnosis in the IRIS® Registry: a comparison between images and ICD-10 codes Chu, Z., Le, K., Leng, T., Borkar, D., Candano, C., Ramakrishnan, A., Khapare, K., Mbagwu, M., Torres, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001052064700057

• FARETINA-DME- Early Treatment Patterns and Outcomes in Patients with Diabetic Macular Edema Treated with Faricimab: an IRIS Registry™Analysis Tabano, D., Borkar, D. S., Garmo, V., Shaia, J. K., Kuo, B., Myers, R., LaPrise, A., Leng, T., Singh, R. P. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053758307317

• FARETINA-AMD- Early Treatment Patterns and Outcomes in Patients with Neovascular Age-Related Macular Degeneration Initiating Faricimab: an IRIS Registry™ Analysis Borkar, D. S., Tabano, D., Garmo, V., Shaia, J. K., Kuo, B., Myers, R., LaPrise, A., Leng, T., Singh, R. P. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053758306161

• Clinical and Ophthalmic Biomarkers of Diabetes Mellitus: A Longitudinal Study of Visual Outcome Huang, F., Yu, M., Huang, L., Zhou, X., Wang, R. K., Leng, T., Wang, S., Liao, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053758307308

• MicroRNA-494 augments fibrotic transformation of human retinal pigment epithelial cells and targets p27 with cell-type specificity. Frontiers in ophthalmology Leng, T., Kamboj, G., Sun, X., Chang, H., Davda, P., Greer, M., Stary, C. M. 2023; 3: 1168650

  Abstract

  Epiretinal membranes (ERMs) are the result of fibro-cellular proliferation that cause distortion and impairment of central vision. We hypothesized that select microRNAs (miRs) regulate retinal fibro-proliferation and ERM formation. Following IRB approval, a pilot study was performed in patients presenting for retina surgery with and without clinical ERMs. Total RNA was isolated from ERM tissue and controls from non-ERM vitreous and subjected to miR profiling via microarray analysis. MiR-494 was identified as the only miR selectively expressed at significantly greater levels, and in silico analysis identified p27 as a putative fibroproliferative gene target of miR-494. In vitro testing of miR-494 and p27 in fibrotic transformation was assessed in spontaneously immortalized human retinal pigment epithelial (RPE) and human Müller cell lines, stimulated to transform into a fibroproliferative state via transforming growth factor beta (TGFβ). Fibroproliferative transformation was characterized by de novo cellular expression of alpha smooth muscle actin (αSMA). In both RPE and Müller cells, both TGFβ and miR-494 mimic decreased p27 expression. In parallel experiments, transfection with p27 siRNA augmented TGFβ-induced αSMA expression, while only in RPE cells did co-transfection with miR-494 inhibitor decrease αSMA levels. These results demonstrate that miR-494 augments fibrotic transformation in both Müller cells and RPEs, however only in RPEs does miR-494 mediate fibrotic transformation via p27. As p27 is known to regulate cellular proliferation and differentiation, future studies should extend clinical testing of miR-494 and/or p27 as a potential novel non-surgical therapy for ERMs, as well as identify relevant miR-494 targets in Müller cells.

  View details for DOI 10.3389/fopht.2023.1168650

  View details for PubMedID 38983004

  View details for PubMedCentralID PMC11182081

• Contrastive learning-based pretraining improves representation and transferability of diabetic retinopathy classification models. Scientific reports Alam, M. N., Yamashita, R., Ramesh, V., Prabhune, T., Lim, J. I., Chan, R. V., Hallak, J., Leng, T., Rubin, D. 2023; 13 (1): 6047

  Abstract

  Diabetic retinopathy (DR) is a major cause of vision impairment in diabetic patients worldwide. Due to its prevalence, early clinical diagnosis is essential to improve treatment management of DR patients. Despite recent demonstration of successful machine learning (ML) models for automated DR detection, there is a significant clinical need for robust models that can be trained with smaller cohorts of dataset and still perform with high diagnostic accuracy in independent clinical datasets (i.e., high model generalizability). Towards this need, we have developed a self-supervised contrastive learning (CL) based pipeline for classification of referable vs non-referable DR. Self-supervised CL based pretraining allows enhanced data representation, therefore, the development of robust and generalized deep learning (DL) models, even with small, labeled datasets. We have integrated a neural style transfer (NST) augmentation in the CL pipeline to produce models with better representations and initializations for the detection of DR in color fundus images. We compare our CL pretrained model performance with two state of the art baseline models pretrained with Imagenet weights. We further investigate the model performance with reduced labeled training data (down to 10 percent) to test the robustness of the model when trained with small, labeled datasets. The model is trained and validated on the EyePACS dataset and tested independently on clinical datasets from the University of Illinois, Chicago (UIC). Compared to baseline models, our CL pretrained FundusNet model had higher area under the receiver operating characteristics (ROC) curve (AUC) (CI) values (0.91 (0.898 to 0.930) vs 0.80 (0.783 to 0.820) and 0.83 (0.801 to 0.853) on UIC data). At 10 percent labeled training data, the FundusNet AUC was 0.81 (0.78 to 0.84) vs 0.58 (0.56 to 0.64) and 0.63 (0.60 to 0.66) in baseline models, when tested on the UIC dataset. CL based pretraining with NST significantly improves DL classification performance, helps the model generalize well (transferable from EyePACS to UIC data), and allows training with small, annotated datasets, therefore reducing ground truth annotation burden of the clinicians.

  View details for DOI 10.1038/s41598-023-33365-y

  View details for PubMedID 37055475

• Identifying the mechanism of missingness for unspecified diabetic retinopathy disease severity in the electronic health record: an IRIS® Registry analysis. Journal of the American Medical Informatics Association : JAMIA Hatfield, M., Nguyen, T. H., Chapman, R., Myrick, A. C., Leng, T., Mbagwu, M., Baxi, S., Torres, A. Z., Borkar, D. S. 2023

  Abstract

  Observational studies of diabetic retinopathy (DR) using electronic health record data often determine disease severity using International Classification of Disease (ICD) codes. We investigated the mechanism of missingness for DR severity based on ICD coding using the American Academy of Ophthalmology IRIS® Registry. We included all patient encounters in the registry with a DR ICD-9 or ICD-10 code between January 1, 2014 and June 30, 2021. Demographic, clinical, and practice-level characteristics were compared between encounters with specified and unspecified disease severity. Practices were divided into quartiles based on the proportion of clinical encounters with unspecified DR severity. Encounters with unspecified disease severity were associated with significantly older patient age, better visual acuity, and lower utilization of ophthalmic procedures. Higher volume practices and retina specialist practices had lower proportions of clinical encounters with unspecified disease severity. Results strongly suggest that DR disease severity related to ICD coding is missing not at random.

  View details for DOI 10.1093/jamia/ocad037

  View details for PubMedID 36928508

• Vitreoretinal Specialist Use of Ancillary Testing: An IRIS® Registry Analysis CLINICAL OPHTHALMOLOGY Vishwakarma, S., Borkar, D. S., Laprise, A., Mbagwu, M., Leng, T. 2023; 17: 3085

  View details for Web of Science ID 001087328300002

• Emulating VIEW 1 and VIEW 2 Clinical Trial Outcome Data Using the American Academy of Ophthalmology IRIS Registry OPHTHALMIC SURGERY LASERS & IMAGING RETINA Gallivan, M. D., Garcia, K. M., Torres, A. Z., Lum, F., Li, C., Mbagwu, M., Leng, T. 2023; 54 (1): 6-+

  Abstract

  A retrospective, noninterventional cohort study of the American Academy of Ophthalmology IRIS Registry, an electronic health record (EHR)-based comprehensive eye disease and condition registry, intended to assess whether the IRIS® Registry (Intelligent Research in Sight) could emulate the VIEW randomized clinical trials (VIEW RCTs) eligibility criteria, treatment protocol regimen, and primary endpoint.Deidentified patients having an anti-VEGF injection of aflibercept or ranibizumab between January 1, 2013, and December 31, 2018, from the IRIS Registry. Patients were treated in accordance with one of three treatment regimens from the VIEW RCT: monthly intravitreal aflibercept injection (IAI 2Q4), intravitreal aflibercept every 2 months after 3 initial monthly doses (IAI 2Q8), or monthly ranibizumab (RQ4) injection. The main outcome measures are the number and proportion of patients meeting VIEW RCT eligibility and treatment group criteria, demographic, and clinical differences between IRIS Registry treatment groups, mean change in best documented visual acuity at one year, and evaluation of the primary endpoint of the VIEW RCT: difference in the proportion of patients maintaining vision.Among the 90,900 patients who met VIEW RCT eligibility criteria, 4,457 (4.85%) met treatment group criteria. The percentage of patients maintaining vision at one year was over 90%. No statistically significant difference was observed when comparing the proportion of patients maintaining vision among the RQ4 treatment group to the IAI 2Q4 or IAI 2Q8 treatment group.A small percentage of real-world patients met VIEW RCT study eligibility criteria and treatment protocol regimen. Among patients meeting all available criteria, the primary endpoint interpretation yielded by an observational EHR-based dataset suggested comparable results to the VIEW RCT. [Ophthalmic Surg Lasers Imaging Retina 2023;54:6-14.].

  View details for DOI 10.3928/23258160-20221214-01

  View details for Web of Science ID 001052416400001

  View details for PubMedID 36626210

• Dry Age-Related Macular Degeneration: Distribution of Visual Acuity and Progression Risk in a Large Registry. Ophthalmology and therapy Leng, T., Schwartz, J., Nimke, D., Gallivan, M., Fevrier, H., Rozario, N., Schultz, N. M. 2022

  Abstract

  INTRODUCTION: Understanding the progression to geographic atrophy (GA) in late dry age-related macular degeneration (dAMD) can support development opportunities for dAMD treatments. We characterized dAMD by distribution of visual acuity (VA) categories and evaluated VA progression risk by disease stage.METHODS: This retrospective observational study used data from the American Academy of Ophthalmology IRIS Registry (Intelligent Research in Sight) to identify patients diagnosed with dAMD in≥1 eye from January 2016 through December 2019 (index date) with≥1 visit and ≥1 VA measurement recorded post-index date. Patients were followed until the date of last visit, last contribution for diagnosing provider, or diagnosis of neovascular AMD post-index. Models were utilized to describe the distribution of VA categories and progression to worsening VA.RESULTS: Data from 593,277patients were analyzed. At baseline, 64.4% had mild disease, 29.4% intermediate, and 2.9%/3.3% had GA with/without subfoveal involvement. Most patients with mild (88.4%) and intermediate (79.7%) disease and GA without subfoveal involvement (57.1%) had baseline VA ≥20/63 inthestudy eye; 72.0% of patients with GA with subfoveal involvement had VA <20/63. Modeled results showed lower VAwithmore progressive stage at baseline.Annual probability ofstable dAMD based on baseline stage ranged from 82.1% (GA without) to 92.3% (GA with subfoveal involvement). Annual progression probability to GA without/with subfoveal involvement was 0.4% for mild and 5.5%forintermediate disease and from dry to neovascular AMD, 0.5% for mild and 8.0% for intermediate disease.CONCLUSIONS: Results from this analysis of a large database of electronic health records complement those from randomized trials and show that patients with more advanced dAMD have lower VA at baseline and that VA progression is generally faster with each progressive stage. Together these findings highlight the disease burden and trajectory of dAMD as well as opportunities for addressing unmet needs.

  View details for DOI 10.1007/s40123-022-00583-y

  View details for PubMedID 36369619

• Depth-resolved extraction of optical attenuation for glaucoma assessment in clinical settings: a pilot study BIOMEDICAL OPTICS EXPRESS Chang, S., Murff, C., Leng, T., Groth, S. L., Bowden, A. K. 2022; 13 (8): 4326-4337

  View details for DOI 10.1364/BOE.461348

  View details for Web of Science ID 000838394800001

• Predicting Systemic Health Features from Retinal Fundus Images Using Transfer-Learning-Based Artificial Intelligence Models. Diagnostics (Basel, Switzerland) Khan, N. C., Perera, C., Dow, E. R., Chen, K. M., Mahajan, V. B., Mruthyunjaya, P., Do, D. V., Leng, T., Myung, D. 2022; 12 (7)

  Abstract

  While color fundus photos are used in routine clinical practice to diagnose ophthalmic conditions, evidence suggests that ocular imaging contains valuable information regarding the systemic health features of patients. These features can be identified through computer vision techniques including deep learning (DL) artificial intelligence (AI) models. We aim to construct a DL model that can predict systemic features from fundus images and to determine the optimal method of model construction for this task. Data were collected from a cohort of patients undergoing diabetic retinopathy screening between March 2020 and March 2021. Two models were created for each of 12 systemic health features based on the DenseNet201 architecture: one utilizing transfer learning with images from ImageNet and another from 35,126 fundus images. Here, 1277 fundus images were used to train the AI models. Area under the receiver operating characteristics curve (AUROC) scores were used to compare the model performance. Models utilizing the ImageNet transfer learning data were superior to those using retinal images for transfer learning (mean AUROC 0.78 vs. 0.65, p-value < 0.001). Models using ImageNet pretraining were able to predict systemic features including ethnicity (AUROC 0.93), age > 70 (AUROC 0.90), gender (AUROC 0.85), ACE inhibitor (AUROC 0.82), and ARB medication use (AUROC 0.78). We conclude that fundus images contain valuable information about the systemic characteristics of a patient. To optimize DL model performance, we recommend that even domain specific models consider using transfer learning from more generalized image sets to improve accuracy.

  View details for DOI 10.3390/diagnostics12071714

  View details for PubMedID 35885619

• Optimal Selection of Longitudinally Measured Imaging Biomarkers Affecting Conversion Time to Neovascular AMD Using a Regularized Multivariate Bayesian Joint Model Sahu, S., De Sisternes, L., Alam, M., Leng, T., Rubin, D., Sun, J., Basu, S., Hallak, J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401300180

• Characterizing real-world functional outcomes in patients with geographic atrophy: An IRIS Registry Analysis Leng, T., Borkar, D. S., Hatfield, M., Li, S., Gallivan, M., Joshi, P., McKeown, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401305079

• A hierarchical optical coherence tomography annotation workflow with crowds and medical experts Zhang, M., Gao, S. S., Steffen, V., Wu, Z., Leng, T., Tehrani, M., Mirsharif, S., Movva, N., Hejrati, M., Chen, H. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844437002065

• Retrospective cohort analysis of patients with geographic atrophy (GA) secondary to age-related macular degeneration followed for 3 years in clinical practice Khan, M., Rahimy, E., Ho, A. C., Corley, R., Gallivan, M., Jones, D., Ribeiro, R., Leng, T., Holekamp, N. M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401300299

• Predicting systemic health features from retinal fundus images using transfer-learning based AI models Khan, N. C., Perera, C., Dow, E. R., Leng, T., Mahajan, V. B., Mruthyunjaya, P., Do, D. V., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844437002058

• Automated machine learning for diagnosis of geographic atrophy and subfoveal involvement using real-world fundus autofluorescence and infrared reflectance images Chu, Z., Mbagwu, M., Borka, D., Ramakrishnan, A., Khapare, K., Candano, C., Torres, A. Z., Kalvaria, H., Roe, M. T., Leng, T. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401303021

• Investigating hyalocyte-like cells in epiretinal membranes using serially acquired optical coherence tomography Soetikno, B., Miller, D., Zhang, H., Goldberg, J. L., Leng, T., Dubra, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844437005173

• Integration of Artificial Intelligence into a Telemedicine-Based Diabetic Retinopathy Screening Program Chen, K., Dow, E. R., Khan, N. C., Levine, M., Perera, C., Phadke, A., Dang, J., Weng, K., Do, D. V., Mahajan, V. B., Mruthyunjaya, P., Mishra, K., Leng, T., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401304101

• Contrastive learning improves representation and transferability of diabetic retinopathy classification models Alam, M., Leng, T., Hallak, J., Rubin, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401303141

• A buoyant mass in the brain: Intraventricular migration of silicone oil. American journal of ophthalmology case reports Guo, L. Y., Jamiolkowski, R. M., Hassan, M., Leng, T. 2022; 25: 101399

  View details for DOI 10.1016/j.ajoc.2022.101399

  View details for PubMedID 35243146

• Ophthalmology and COVID-19: The Impact of the Pandemic on Patient Care and Outcomes: An IRIS (R) Registry Study OPHTHALMOLOGY Leng, T., Gallivan, M. D., Kras, A., Lum, F., Roe, M. T., LI, C., Parke II, D. W., Schwartz, S. D. 2021; 128 (12): 1782-1784

  View details for Web of Science ID 000720933000020

• Ocular adverse events following intravitreal brolucizumab for neovascular age-related macular degeneration at a single tertiary care center. European journal of ophthalmology Nguyen, H. V., Li, A. S., Silva, A. R., Leng, T. 2021: 11206721211059332

  Abstract

  PURPOSE: To determine the incidence of ocular adverse effects (AEs) following brolucizumab injection for neovascular age-related macular degeneration at a tertiary academic institution.DESIGN: Retrospective, single center cohort study.PARTICIPANTS: All patients who received an intravitreal injection of brolucizumab 6 mg for neovascular age-related macular degeneration between October 7, 2019 and July 31, 2020.METHODS: Medical records of all patients who received brolucizumab 6 mg during the aforementioned time period were carefully reviewed and all ocular adverse effects after injection were charted.MAIN OUTCOME MEASURES: Incidence of post-injection ocular AEs, including intraocular inflammation (IOI), and time to development of AEs after injection.RESULTS: A total of 77 patients received brolucizumab 6 mg for a total of 115 administrations during the study period. There were 4 AEs (3.5%), including three cases of IOI (2.6%), one central retinal artery occlusion, and one retinal detachment. Two men and two women were affected.CONCLUSION: Ocular AEs, including those leading to severe vision loss, may develop after intravitreal brolucizumab 6 mg. A careful discussion of benefits and risks to brolucizumab should be conducted with all patients.PRECIS: In this first case series of ocular adverse effects after brolucizumab 6 mg injection at a single tertiary care center, the incidence of ocular adverse effects was 3.5%, including a 2.6% incidence of intraocular inflammation.

  View details for DOI 10.1177/11206721211059332

  View details for PubMedID 34761684

• Artificial intelligence and ophthalmic surgery CURRENT OPINION IN OPHTHALMOLOGY Mishra, K., Leng, T. 2021; 32 (5): 425-430

  View details for DOI 10.1097/ICU.0000000000000788

  View details for Web of Science ID 000680565900006

• Artificial intelligence and ophthalmic surgery. Current opinion in ophthalmology Mishra, K., Leng, T. 2021; 32 (5): 425-430

  Abstract

  Artificial intelligence and deep learning have become important tools in extracting data from ophthalmic surgery to evaluate, teach, and aid the surgeon in all phases of surgical management. The purpose of this review is to highlight the ever-increasing intersection of computer vision, machine learning, and ophthalmic microsurgery.Deep learning algorithms are being applied to help evaluate and teach surgical trainees. Artificial intelligence tools are improving real-time surgical instrument tracking, phase segmentation, as well as enhancing the safety of robotic-assisted vitreoretinal surgery.Similar to strides appreciated in ophthalmic medical disease, artificial intelligence will continue to become an important part of surgical management of ocular conditions. Machine learning applications will help push the boundaries of what surgeons can accomplish to improve patient outcomes.

  View details for DOI 10.1097/ICU.0000000000000788

  View details for PubMedID 34397576

• Foundational Considerations for Artificial Intelligence Utilizing Ophthalmic Images. Ophthalmology Abramoff, M. D., Cunningham, B., Patel, B., Eydelman, M. B., Leng, T., Sakamoto, T., Blodi, B., Grenon, S. M., Wolf, R. M., Manrai, A. K., Ko, J. M., Chiang, M. F., Char, D., Collaborative Community on Ophthalmic Imaging Executive Committee and Foundational Principles of Ophthalmic Imaging and Algorithmic Interpretation Working Group 2021

  Abstract

  IMPORTANCE: The development of Artificial Intelligence (AI) and other machine diagnostic systems, also known as Software as a Medical Device (SaMD), and its recent introduction into clinical practice, requires a deeply-rooted foundation in bioethics, for consideration by regulatory agencies and other stakeholders around the globe.OBJECTIVES: Initiate a dialogue on the issues to consider when developing a bioethically sound foundation for AI in medicine, based on images of eye structures, for discussion with all stakeholders.EVIDENCE REVIEW: The scope of the issues and summaries of the discussions under consideration by the Foundational Principles of Ophthalmic Imaging and Algorithmic Interpretation Working Group, as first presented during the Collaborative Community on Ophthalmic Imaging inaugural meeting on September 7, 2020, and afterwards in the working group.FINDINGS: AI has the potential to fundamentally improve the access to healthcare and patient outcomes, while decreasing disparities, lowering cost, as well as enhancing the care team. Nevertheless, substantial concerns exist. Ethicists, AI algorithm experts, as well as the Food and Drug Administration (FDA) and other regulatory agencies, industry, patient advocacy groups, clinicians and their professional societies, other provider groups, payors, and other healthcare stakeholders working together in collaborative communities to resolve such issues as non-maleficence, autonomy and equity, is essential to attain this potential, and impacts all levels of the design, validation and implementation of AI in medicine. Design, validation and implementation of AI warrant meticulous attention.CONCLUSIONS AND RELEVANCE: The development of a bioethically sound foundation may be possible if it is based in non-maleficence, autonomy and equity, for considerations for the design, validation and implementation for AI systems. Achieving such a foundation will be helpful for continuing successful introduction into medicine, before consideration by regulatory agencies around the globe.Fundamental improvements in accessibility and quality of healthcare, decrease in health disparities, and lower cost can thereby be achieved. These considerations should be discussed with all stakeholders and expanded upon as a useful initiation of this dialogue.

  View details for DOI 10.1016/j.ophtha.2021.08.023

  View details for PubMedID 34478784

• Imaging and artificial intelligence for progression of age-related macular degeneration. Experimental biology and medicine (Maywood, N.J.) Romond, K., Alam, M., Kravets, S., Sisternes, L. d., Leng, T., Lim, J. I., Rubin, D., Hallak, J. A. 2021: 15353702211031547

  Abstract

  Age-related macular degeneration (AMD) is a leading cause of severe vision loss. With our aging population, it may affect 288 million people globally by the year 2040. AMD progresses from an early and intermediate dry form to an advanced one, which manifests as choroidal neovascularization and geographic atrophy. Conversion to AMD-related exudation is known as progression to neovascular AMD, and presence of geographic atrophy is known as progression to advanced dry AMD. AMD progression predictions could enable timely monitoring, earlier detection and treatment, improving vision outcomes. Machine learning approaches, a subset of artificial intelligence applications, applied on imaging data are showing promising results in predicting progression. Extracted biomarkers, specifically from optical coherence tomography scans, are informative in predicting progression events. The purpose of this mini review is to provide an overview about current machine learning applications in artificial intelligence for predicting AMD progression, and describe the various methods, data-input types, and imaging modalities used to identify high-risk patients. With advances in computational capabilities, artificial intelligence applications are likely to transform patient care and management in AMD. External validation studies that improve generalizability to populations and devices, as well as evaluating systems in real-world clinical settings are needed to improve the clinical translations of artificial intelligence AMD applications.

  View details for DOI 10.1177/15353702211031547

  View details for PubMedID 34404252

• A Multitask Deep-Learning System to Classify Diabetic Macular Edema for Different Optical Coherence Tomography Devices: A Multicenter Analysis. Diabetes care Tang, F., Wang, X., Ran, A., Chan, C. K., Ho, M., Yip, W., Young, A. L., Lok, J., Szeto, S., Chan, J., Yip, F., Wong, R., Tang, Z., Yang, D., Ng, D. S., Chen, L. J., Brelen, M., Chu, V., Li, K., Lai, T. H., Tan, G. S., Ting, D. S., Huang, H., Chen, H., Ma, J. H., Tang, S., Leng, T., Kakavand, S., Mannil, S. S., Chang, R. T., Liew, G., Gopinath, B., Lai, T. Y., Pang, C. P., Scanlon, P. H., Wong, T. Y., Tham, C. C., Chen, H., Heng, P., Cheung, C. Y. 2021

  Abstract

  OBJECTIVE: Diabetic macular edema (DME) is the primary cause of vision loss among individuals with diabetes mellitus (DM). We developed, validated, and tested a deep learning (DL) system for classifying DME using images from three common commercially available optical coherence tomography (OCT) devices.RESEARCH DESIGN AND METHODS: We trained and validated two versions of a multitask convolution neural network (CNN) to classify DME (center-involved DME [CI-DME], non-CI-DME, or absence of DME) using three-dimensional (3D) volume scans and 2D B-scans, respectively. For both 3D and 2D CNNs, we used the residual network (ResNet) as the backbone. For the 3D CNN, we used a 3D version of ResNet-34 with the last fully connected layer removed as the feature extraction module. A total of 73,746 OCT images were used for training and primary validation. External testing was performed using 26,981 images across seven independent data sets from Singapore, Hong Kong, the U.S., China, and Australia.RESULTS: In classifying the presence or absence of DME, the DL system achieved area under the receiver operating characteristic curves (AUROCs) of 0.937 (95% CI 0.920-0.954), 0.958 (0.930-0.977), and 0.965 (0.948-0.977) for the primary data set obtained from CIRRUS, SPECTRALIS, and Triton OCTs, respectively, in addition to AUROCs >0.906 for the external data sets. For further classification of the CI-DME and non-CI-DME subgroups, the AUROCs were 0.968 (0.940-0.995), 0.951 (0.898-0.982), and 0.975 (0.947-0.991) for the primary data set and >0.894 for the external data sets.CONCLUSIONS: We demonstrated excellent performance with a DL system for the automated classification of DME, highlighting its potential as a promising second-line screening tool for patients with DM, which may potentially create a more effective triaging mechanism to eye clinics.

  View details for DOI 10.2337/dc20-3064

  View details for PubMedID 34315698

• Ophthalmology and COVID-19: The Impact of the Pandemic on Patient Care and Outcomes-an IRIS Registry Study. Ophthalmology Leng, T., Gallivan, M. D., Kras, A., Lum, F., Roe, M. T., Li, C., Parke, D. W., Schwartz, S. D. 2021

  View details for DOI 10.1016/j.ophtha.2021.06.011

  View details for PubMedID 34144077

• Probabilistic Forecasting of Anti-VEGF Treatment Frequency in Neovascular Age-Related Macular Degeneration. Translational vision science & technology Pfau, M., Sahu, S., Rupnow, R. A., Romond, K., Millet, D., Holz, F. G., Schmitz-Valckenberg, S., Fleckenstein, M., Lim, J. I., de Sisternes, L., Leng, T., Rubin, D. L., Hallak, J. A. 2021; 10 (7): 30

  Abstract

  Purpose: To probabilistically forecast needed anti-vascular endothelial growth factor (anti-VEGF) treatment frequency using volumetric spectral domain-optical coherence tomography (SD-OCT) biomarkers in neovascular age-related macular degeneration from real-world settings.Methods: SD-OCT volume scans were segmented with a custom deep-learning-based analysis pipeline. Retinal thickness and reflectivity values were extracted for the central and the four inner Early Treatment Diabetic Retinopathy Study (ETDRS) subfields for six retinal layers (inner retina, outer nuclear layer, inner segments [IS], outer segments [OS], retinal pigment epithelium-drusen complex [RPEDC] and the choroid). Machine-learning models were probed to predict the anti-VEGF treatment frequency within the next 12 months. Probabilistic forecasting was performed using natural gradient boosting (NGBoost), which outputs a full probability distribution. The mean absolute error (MAE) between the predicted versus actual anti-VEGF treatment frequency was the primary outcome measure.Results: In a total of 138 visits of 99 eyes with neovascular AMD (96 patients) from two clinical centers, the prediction of future anti-VEGF treatment frequency was observed with an accuracy (MAE [95% confidence interval]) of 2.60 injections/year [2.25-2.96] (R2 = 0.390) using random forest regression and 2.66 injections/year [2.31-3.01] (R2 = 0.094) using NGBoost, respectively. Prediction intervals were well calibrated and reflected the true uncertainty of NGBoost-based predictions. Standard deviation of RPEDC-thickness in the central ETDRS-subfield constituted an important predictor across models.Conclusions: The proposed, fully automated pipeline enables probabilistic forecasting of future anti-VEGF treatment frequency in real-world settings.Translational Relevance: Prediction of a probability distribution allows the physician to inspect the underlying uncertainty. Predictive uncertainty estimates are essential to highlight cases where human-inspection and/or reversion to a fallback alternative is warranted.

  View details for DOI 10.1167/tvst.10.7.30

  View details for PubMedID 34185055

• AAO IRIS Registry data replicates VIEW 1 and VIEW 2 clinical trial outcome data Leng, T., Xu, J., Kras, A., Wood, K., Doriswami, R., Shadra, C., Torres, A., Li, C., Lum, F. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690760500343

• A Multi-Task Deep-Learning System to Classify Diabetic Macular Edema for Different Optical Coherence Tomography Devices: A Multi-Center Analysis Cheung, C., Tang, F., Ran, A., Tan, G., Ting, D. W., Chen, H., Ma, H., Tang, S., Leng, T., Kakavand, S., Mannil, S. S., Chang, R., Liew, G., Gopinath, B., Wong, T. Y., Wang, X. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690761100112

• Extending interoperability in ophthalmology through Fast Healthcare Interoperability Resource (FHIR) Kras, A., Oliver, W., Gillies, M. C., Mair, M., Chu, S., Morlet, N., Mbagwu, M., Hwang, T. S., Roe, M., Leng, T. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690761100787

• Large Scale Cross-Vendor Linkage of Ophthalmic Imaging and American Academy of Ophthalmology IRIS (R) Registry Clinical Data Mbagwu, M., Leng, T., Luthra, A., Borkar, D., Kras, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690761400447

• Visual acuity and progression of macular atrophy in patients receiving intravitreal anti-VEGF for age-related macular degeneration. European journal of ophthalmology Ji, M. H., Callaway, N. F., Ludwig, C. A., Vail, D., Al-Moujahed, A., Rosenblatt, T. R., Leng, T., Sanislo, S. R., Moshfeghi, D. M. 2021: 11206721211001708

  Abstract

  PURPOSE: Whether intravitreal anti-vascular endothelial growth factors (VEGFs) cause retinal atrophy is still a subject of debate. We reported 13 eyes that received several injections of anti-VEGF for wet age-related macular degeneration (AMD) with good visual acuity despite geographic atrophy on imaging.METHODS: This is a case series study conducted at Byers Eye Institute at Stanford University. Patients of three retina specialists with wet AMD who received six or more intravitreal injection of anti-VEGFs with visual acuity of 20/60 or better and incomplete RPE and outer retina atrophy (iRORA) or complete RPE and outer retinal atrophy (cRORA) were enrolled in this case series. Different imaging modalities were reviewed by three retina specialists comparing the baseline with the most recent exam.RESULTS: About 13 eyes of 10 patients met the selection criteria. Eleven eyes were classified as iRORA and 2 as cRORA. Despite the development of macular atrophy on imaging after an average of 38.1 injections, eyes maintained stable visual acuity.CONCLUSION: The discrepancy between structural and functional findings in this cohort suggests that patients treated by anti-VEGF drugs exhibit divergent clinical outcomes for currently unknown reasons. The authors propose anti-VEGF may affect melanosomes within RPE without disrupting RPE and photoreceptors function completely. This requires further investigation.

  View details for DOI 10.1177/11206721211001708

  View details for PubMedID 33781106

• Management of repository corticotropin injection therapy for non-infectious uveitis: a Delphi study ACTA OPHTHALMOLOGICA Nguyen, Q., Anesi, S. D., Chexal, S., Chu, D. S., Dayani, P. N., Leng, T., Meleth, A. D., Sallam, A. A., Sheppard, J. D., Silverstein, S. M., Toyos, M., Wang, R. C., Foster, C. 2021

  Abstract

  Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases.The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree).The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission ≥ 2 years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent.Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.

  View details for DOI 10.1111/aos.14702

  View details for Web of Science ID 000626812100001

  View details for PubMedID 33751822

• Frequency of Urgent or Emergent Vitreoretinal Surgical Procedures in the United States During the COVID-19 Pandemic. JAMA ophthalmology Breazzano, M. P., Nair, A. A., Arevalo, J. F., Barakat, M. R., Berrocal, A. M., Chang, J. S., Chen, A. n., Eliott, D. n., Garg, S. J., Ghadiali, Q. n., Gong, D. n., Grewal, D. S., Handa, J. T., Henderson, M. n., Leiderman, Y. I., Leng, T. n., Mannina, A. n., Mendel, T. A., Mustafi, D. n., de Koo, L. C., Patel, S. N., Patel, T. P., Prenner, J. n., Richards, P. n., Singh, R. P., Wykoff, C. C., Yannuzzi, N. A., Yu, H. n., Modi, Y. S., Chang, S. n. 2021

  Abstract

  The American Academy of Ophthalmology (AAO) indicated that urgent or emergent vitreoretinal surgical procedures should continue during the coronavirus disease 2019 (COVID-19) pandemic. Although decreases in the frequency of critical procedures have been reported outside the field of ophthalmology, analyses are limited by volume, geography, and time.To evaluate whether the frequency of ophthalmic surgical procedures deemed urgent or emergent by the AAO changed across the United States during the COVID-19 pandemic.Vitreoretinal practices from 17 institutions throughout the US participated in this multicenter cross-sectional study. The frequency of 11 billed vitreoretinal Current Procedural Terminology (CPT) codes across respective weeks was obtained from each practice between January 1, 2019, and May 31, 2020. Data were clustered into intravitreal injections (code 67028), lasers and cryotherapy (codes 67141, 67145, and 67228), retinal detachment (RD) repairs (codes 67107, 67108, 67110, and 67113), and other vitrectomies (codes 67036, 67039, and 67040). Institutions were categorized by region (Northeast, Midwest, South, and West Coast), practice setting (academic [tax-exempt] or private [non-tax-exempt]), and date of respective statewide stay-at-home orders.Nationwide changes in the frequency of billing for urgent or emergent vitreoretinal surgical procedures during the COVID-19 pandemic.A total of 526 536 CPT codes were ascertained: 483 313 injections, 19 257 lasers or cryotherapy, 14 949 RD repairs, and 9017 other vitrectomies. Relative to 2019, a weekly institutional decrease in injections was observed from March 30 to May 2, 2020, with a maximal 38.6% decrease (from a mean [SD] of 437.8 [436.3] to 273.8 [269.0] injections) from April 6 to 12, 2020 (95% CI, -259 to -69 injections; P = .002). A weekly decrease was also identified that spanned a longer interval, at least until study conclusion (March 16 to May 31, 2020), for lasers and cryotherapy, with a maximal 79.6% decrease (from a mean [SD] of 6.6 [7.7] to 1.5 [2.0] procedures) from April 6 to 12, 2020 (95% CI, -6.8 to -3.3 procedures; P < .001), for RD repairs, with a maximal 59.4% decrease (from a mean [SD] of 3.5 [4.0] to 1.6 [2.2] repairs) from April 13 to 19, 2020 (95% CI, -2.7 to -1.4 repairs; P < .001), and for other vitrectomies, with a maximal 84.3% decrease (from a mean [SD] of 3.0 [3.1] to 0.4 [0.8] other vitrectomies) from April 6 to 12, 2020 (95% CI, -3.3 to -1.8 other vitrectomies; P < .001). No differences were identified by region, setting, or state-level stay-at-home order adjustment.Although the AAO endorsed the continued performance of urgent or emergent vitreoretinal surgical procedures, the frequency of such procedures throughout the country experienced a substantial decrease that may persist after the COVID-19 pandemic's initial exponential growth phase. This decrease appears independent of region, setting, and state-level stay-at-home orders. It is unknown to what extent vitreoretinal intervention would have decreased without AAO recommendations, and how the decrease is associated with outcomes. Although safety is paramount during the COVID-19 pandemic, practices should consider prioritizing availability for managing high-acuity conditions until underlying reasons for the reduction are fully appreciated.

  View details for DOI 10.1001/jamaophthalmol.2021.0036

  View details for PubMedID 33662093

• Automatic Identification of Referral-Warranted Diabetic Retinopathy Using Deep Learning on Mobile Phone Images. Translational vision science & technology Ludwig, C. A., Perera, C., Myung, D., Greven, M. A., Smith, S. J., Chang, R. T., Leng, T. 2020; 9 (2): 60

  Abstract

  Purpose: To evaluate the performance of a deep learning algorithm in the detection of referral-warranted diabetic retinopathy (RDR) on low-resolution fundus images acquired with a smartphone and indirect ophthalmoscope lens adapter.Methods: An automated deep learning algorithm trained on 92,364 traditional fundus camera images was tested on a dataset of smartphone fundus images from 103 eyes acquired from two previously published studies. Images were extracted from live video screenshots from fundus examinations using a commercially available lens adapter and exported as a screenshot from live video clips filmed at 1080p resolution. Each image was graded twice by a board-certified ophthalmologist and compared to the output of the algorithm, which classified each image as having RDR (moderate nonproliferative DR or worse) or no RDR.Results: In spite of the presence of multiple artifacts (lens glare, lens particulates/smudging, user hands over the objective lens) and low-resolution images achieved by users of various levels of medical training, the algorithm achieved a 0.89 (95% confidence interval [CI] 0.83-0.95) area under the curve with an 89% sensitivity (95% CI 81%-100%) and 83% specificity (95% CI 77%-89%) for detecting RDR on mobile phone acquired fundus photos.Conclusions: The fully data-driven artificial intelligence-based grading algorithm herein can be used to screen fundus photos taken from mobile devices and identify with high reliability which cases should be referred to an ophthalmologist for further evaluation and treatment.Translational Relevance: The implementation of this algorithm on a global basis could drastically reduce the rate of vision loss attributed to DR.

  View details for DOI 10.1167/tvst.9.2.60

  View details for PubMedID 33294301

• MS-CAM: Multi-Scale Class Activation Maps for Weakly-Supervised Segmentation of Geographic Atrophy Lesions in SD-OCT Images IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS Ma, X., Ji, Z., Niu, S., Leng, T., Rubin, D. L., Chen, Q. 2020; 24 (12): 3443–55

  Abstract

  As one of the most critical characteristics in advanced stage of non-exudative Age-related Macular Degeneration (AMD), Geographic Atrophy (GA) is one of the significant causes of sustained visual acuity loss. Automatic localization of retinal regions affected by GA is a fundamental step for clinical diagnosis. In this paper, we present a novel weakly supervised model for GA segmentation in Spectral-Domain Optical Coherence Tomography (SD-OCT) images. A novel Multi-Scale Class Activation Map (MS-CAM) is proposed to highlight the discriminatory significance regions in localization and detail descriptions. To extract available multi-scale features, we design a Scaling and UpSampling (SUS) module to balance the information content between features of different scales. To capture more discriminative features, an Attentional Fully Connected (AFC) module is proposed by introducing the attention mechanism into the fully connected operations to enhance the significant informative features and suppress less useful ones. Based on the location cues, the final GA region prediction is obtained by the projection segmentation of MS-CAM. The experimental results on two independent datasets demonstrate that the proposed weakly supervised model outperforms the conventional GA segmentation methods and can produce similar or superior accuracy comparing with fully supervised approaches. The source code has been released and is available on GitHub: https://github.com/ jizexuan/Multi-Scale-Class-Activation-Map-Tensorflow.

  View details for DOI 10.1109/JBHI.2020.2999588

  View details for Web of Science ID 000597173000011

  View details for PubMedID 32750923

• An integrated time adaptive geographic atrophy prediction model for SD-OCT images. Medical image analysis Zhang, Y., Zhang, X., Ji, Z., Niu, S., Leng, T., Rubin, D. L., Yuan, S., Chen, Q. 2020; 68: 101893

  Abstract

  The automated prediction of geographic atrophy (GA) lesion growth can help ophthalmologists understand how the GA progresses, and assess the efficiency of current treatment and the prognosis of the disease. We developed an integrated time adaptive prediction model for identifying the location of future GA growth. The proposed model was comprised of bi-directional long short-term memory (BiLSTM) network-based prediction module and convolutional neural network (CNN)-based refinement module. Considering the discontinuity of time intervals among sequential follow-up visits, we integrated time factors into BiLSTM-based prediction module to control the time attribute expediently. Then, the results from prediction module were refined by a CNN-based strategy to obtain the final locations of future GA growth. The 10 scenarios were designed to evaluate the prediction accuracy of our proposed model. The 1-6th scenarios demonstrated the importance of the prior information similarity, the 7-8th scenarios verified the effect of time factors and refinement methods respectively and the 9th scenario compared the prediction results between those using a single follow-up visit for training and using 2 sequential follow-up visits for training. The 10th scenario showed the model generalization performance across regions. The average dice indexes (DI) of the predicted GA regions in the 1-6th scenarios are 0.86, 0.89, 0.89, 0.92 and 0.88, 0.90, respectively. By integrating time factors to the BiLSTM models, the prediction accuracy was improved by almost 10%. The CNN-based refinement strategy can remove the wrong GA regions effectively to preserve the actual GA regions and improve the prediction accuracy further. The prediction results based on 2 sequential follow-up visits showed higher correlations than that based on single follow-up visit. The proposed model presented a good generalization performance while training patients and testing patients were from different regions. Experimental results demonstrated the importance of prior information to the prediction accuracy. We demonstrate the feasibility of creating a model for disease prediction.

  View details for DOI 10.1016/j.media.2020.101893

  View details for PubMedID 33260118

• Rationale for American Society of Retina Specialists Best Practice Recommendations for Conducting Vitreoretinal Surgery during the COVID-19 Era. Journal of vitreoretinal diseases Chao, D. L., Sridhar, J., Kuriyan, A. E., Leng, T., Barnett, B. P., Carlin, A. F., Wykoff, C. C., Gayer, S., Mruthyunjaya, P., Yonekawa, Y., Fawzi, A. A., Berrocal, A. M., Yeh, S., Ting, D., Modi, Y., Zacks, D. N., Yannuzzi, N., Afshari, N. A., Murray, T. 2020; 4 (5): 420-429

  Abstract

  Purpose: To detail the rationale behind recommendations recently published by the American Society of Retina Specialists (ASRS) outlining best practices for safety of vitreoretinal surgeons and staff while performing vitreoretinal surgery during the coronavirus disease (COVID)-19 pandemic.Methods: The committee for ASRS Best Practices for Retinal Surgery during the COVID-19 Pandemic reviewed existing evidence and information on SARS-CoV-2 transmission, and risk factors during vitreoretinal surgery. Recommendations were based on best available published data, cumulative clinical experiences, and recommendations and policies from other organizations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the strength of recommendations and confidence in the evidence. These serve as interim recommendations which are routinely updated given gaps of knowledge and lack of high-quality data on this evolving subject.Results: Relevant existing literature related to methods of transmission, and ocular manifestations of SARS-CoV-2 are summarized. The data and clinical experiences driving recommendations for pre-operative, intraoperative and post-operative surgical considerations, anesthesia choice, as well as considerations for intravitreal injections are provided.Conclusion: Recommendations are provided with the goal of protecting vitreoretinal surgeons and associated personnel from exposure to SARS-CoV-2 during interventional vitreoretinal procedures. This is a rapidly evolving topic with numerous remaining gaps in our current knowledge. As such, recommendations will evolve and the current manuscript is intended to serve as a foundation for continued dialogue on best practices.

  View details for DOI 10.1177/2474126420941707

  View details for PubMedID 34222758

• Prediction of age-related macular degeneration disease using a sequential deep learning approach on longitudinal SD-OCT imaging biomarkers. Scientific reports Banerjee, I., de Sisternes, L., Hallak, J. A., Leng, T., Osborne, A., Rosenfeld, P. J., Gregori, G., Durbin, M., Rubin, D. 2020; 10 (1): 15434

  Abstract

  We propose a hybrid sequential prediction model called "Deep Sequence", integrating radiomics-engineered imaging features, demographic, and visual factors, with a recursive neural network (RNN) model in the same platform to predict the risk of exudation within a future time-frame in non-exudative AMD eyes. The proposed model provides scores associated with risk of exudation in the short term (within 3months) and long term (within 21months), handling challenges related to variability of OCT scan characteristics and the size of the training cohort. We used a retrospective clinical trial dataset that includes 671 AMD fellow eyes with 13,954 observations before any signs of exudation for training and validation in a tenfold cross validation setting. Deep Sequence achieved high performance for the prediction of exudation within 3months (0.96±0.02 AUCROC) and within 21months (0.97±0.02 AUCROC) on cross-validation. Training the proposed model on this clinical trial dataset and testing it on an external real-world clinical dataset showed high performance for the prediction within 3-months (0.82 AUCROC) but a clear decrease in performance for the prediction within 21-months (0.68 AUCROC). While performance differences at longer time intervals may be derived from dataset differences, we believe that the high performance and generalizability achieved in short-term predictions may have a high clinical impact allowing for optimal patient follow-up, adding the possibility of more frequent, detailed screening and tailored treatments for those patients with imminent risk of exudation.

  View details for DOI 10.1038/s41598-020-72359-y

  View details for PubMedID 32963300

• Multilayer atrophy progression in eyes with geographic atrophy secondary to age-related macular degeneration Pfau, M., von der Emde, L., De Sisternes, L., Hallak, J., Leng, T., Schmitz-Valckenberg, S., Holz, F. G., Fleckenstein, M., Rubin, D. L. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554495703290

• The Machines Are Coming: Implications for Image Reading Centers of the Future OPHTHALMOLOGY Leng, T. 2020; 127 (6): 802–3

  View details for DOI 10.1016/j.ophtha.2020.03.003

  View details for Web of Science ID 000553874500015

  View details for PubMedID 32444019

• Two-year outcomes of patients receiving anti-VEGF treatment for neovascular age-related macular degeneration on a treat-and-extend regimen Eng, V., Leng, T. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554528302341

• Fully-automated prediction of anti-VEGF treatment using imaging biomarkers in neovascular age-related macular degeneration Hallak, J., Pfau, M., De Sisternes, L., Rupnow, R., Baker, J., Leng, T., Rubin, D. L. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554528303032

• Automated and Computer-Assisted Detection, Classification, and Diagnosis of Diabetic Retinopathy. Telemedicine journal and e-health : the official journal of the American Telemedicine Association Abramoff, M. D., Leng, T., Ting, D. S., Rhee, K., Horton, M. B., Brady, C. J., Chiang, M. F. 2020

  Abstract

  Background: The introduction of artificial intelligence (AI) in medicine has raised significant ethical, economic, and scientific controversies. Introduction: Because an explicit goal of AI is to perform processes previously reserved for human clinicians and other health care personnel, there is justified concern about the impact on patient safety, efficacy, equity, and liability. Discussion: Systems for computer-assisted and fully automated detection, triage, and diagnosis of diabetic retinopathy (DR) from retinal images show great variation in design, level of autonomy, and intended use. Moreover, the degree to which these systems have been evaluated and validated is heterogeneous. We use the term DR AI system as a general term for any system that interprets retinal images with at least some degree of autonomy from a human grader. We put forth these standardized descriptors to form a means to categorize systems for computer-assisted and fully automated detection, triage, and diagnosis of DR. The components of the categorization system include level of device autonomy, intended use, level of evidence for diagnostic accuracy, and system design. Conclusion: There is currently minimal empirical basis to assert that certain combinations of autonomy, accuracy, or intended use are better or more appropriate than any other. Therefore, at the current stage of development of this document, we have been descriptive rather than prescriptive, and we treat the different categorizations as independent and organized along multiple axes.

  View details for DOI 10.1089/tmj.2020.0008

  View details for PubMedID 32209008

• Rapid Fluctuation of Subretinal Fluid on Encorafenib and Binimetinib. Retina (Philadelphia, Pa.) Li, A. S., Leng, T. n., Nagpal, S. n., Liao, Y. J. 2020

  View details for DOI 10.1097/IAE.0000000000002965

  View details for PubMedID 32833784

• Effect of Human Central Nervous System Stem Cell Subretinal Transplantation on Progression of Geographic Atrophy Secondary to Non Neovascular Age-Related Macular Degeneration. Ophthalmology. Retina Nittala, M. G., Uji, A. n., Velaga, S. B., Hariri, A. H., Naor, J. n., Birch, D. G., Spencer, R. n., Leng, T. n., Capela, A. n., Tsukamoto, A. n., Ip, M. n., Sadda, S. R. 2020

  Abstract

  To evaluate the effect of subretinally transplanted human central nervous system stem cells (HuCNS-SC) on progression of geographic atrophy (GA) in subjects with non-neovascular age-related macular degeneration (NNVAMD).Multicenter, prospective Phase I open-label clinical trial.Fifteen subjects with bilateral GA due solely to AMD.The eye with the worst best-corrected visual acuity from each subject was selected for treatment and considered the study eye; fellow eyes acted as controls. A total of 0.25 X 106 or 1.0 X 106 HuCNS-SC cells were directly infused into the subretinal space, superotemporal to the fovea near the junctional zone outside the area of GA. All subjects underwent spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging using the Spectralis HRA+OCT (Heidelberg Engineering Inc., Germany). Total GA area in both eyes was measured at baseline and month 12 by certified reading center graders using the Spectralis Region Finder software. Sectoral (clock hour)/directional radial GA progression rates with respect to the foveal center in both eyes were calculated using the polar transformation method in Image J. To facilitate comparative analysis across the cohort all eyes were transformed to a right eye orientation.Total GA area and sectoral/directional GA progression rates were compared in both study and control eyes.There was no statistically significant difference in mean change in total GA area at month 12 between study and fellow eyes (1.07 ± 0.84 vs. 2.08 ± 1.97 mm2, P=0.08). Whereas, the month 12 sectoral/directional radial GA growth rate for the superotemporal region (i.e. the location of HuCNS-SC cells transplantation) showed a significantly slower progression rate in study eyes than in fellow eyes (0.29 ± 0.58 vs. 1.08 ± 0.65 mm, P=0.007). The progression rate in the superotemporal quadrant of the study eye was significantly slower than in the other three quadrants combined (P=0.04) CONCLUSIONS: In this small pilot study, HuCNS-SC transplantation appeared associated with slower expansion of the GA lesion in the transplanted quadrant. Larger confirmatory studies are required. Sectoral or directional analysis of growth rates of GA may be a useful approach for assessing the efficacy of locally-delivered therapies.

  View details for DOI 10.1016/j.oret.2020.06.012

  View details for PubMedID 32562884

• Subthreshold laser therapy for macular oedema from branch retinal vein occlusion: focused review. The British journal of ophthalmology Eng, V. A., Leng, T. n. 2020

  Abstract

  Retinal vein occlusion is the second-leading cause of vision loss by retinal vascular disease. Subthreshold micropulse laser therapy (SLT) is safer than conventional laser photocoagulation (CLP), yet existing reviews of its use for branch retinal vein occlusion (BRVO) are limited in scope. A literature search of PubMed, Google Scholar, Embase, Cochrane Library and ClinicalTrials.gov databases was conducted in August 2019 without restriction on language or publication date. Outcomes included changes in macular oedema (ME) and visual acuity (VA), and rates of complications or retreatments. Fourteen studies involving 315-405 eyes diagnosed with BRVO were evaluated. Treatment with SLT is associated with significant and durable reduction of ME and VA as early as 1 month. SLT performs comparably with conventional photocoagulation and intravitreal injections (IVIs) of ranibizumab. Subthreshold laser therapy is safer and as effective as CLP for the treatment of ME associated with BRVO. SLT may be used in combination with anti-VEGF IVIs to enhance improvement in VA and ME resolution.

  View details for DOI 10.1136/bjophthalmol-2019-315192

  View details for PubMedID 32034007

• Progression of Photoreceptor Degeneration in Geographic Atrophy Secondary to Age-related Macular Degeneration. JAMA ophthalmology Pfau, M. n., von der Emde, L. n., de Sisternes, L. n., Hallak, J. A., Leng, T. n., Schmitz-Valckenberg, S. n., Holz, F. G., Fleckenstein, M. n., Rubin, D. L. 2020

  Abstract

  Sensitive outcome measures for disease progression are needed for treatment trials in geographic atrophy (GA) secondary to age-related macular degeneration (AMD).To quantify photoreceptor degeneration outside regions of GA in eyes with nonexudative AMD, to evaluate its association with future GA progression, and to characterize its spatio-temporal progression.Monocenter cohort study (Directional Spread in Geographic Atrophy [NCT02051998]) and analysis of data from a normative data study at a tertiary referral center. One hundred fifty-eight eyes of 89 patients with a mean (SD) age of 77.7 (7.1) years, median area of GA of 8.87 mm2 (IQR, 4.09-15.60), and median follow-up of 1.1 years (IQR, 0.52-1.7 years), as well as 93 normal eyes from 93 participants.Longitudinal spectral-domain optical coherence tomography (SD-OCT) volume scans (121 B-scans across 30° × 25°) were segmented with a deep-learning pipeline and standardized in a pointwise manner with age-adjusted normal data (z scores). Outer nuclear layer (ONL), photoreceptor inner segment (IS), and outer segment (OS) thickness were quantified along evenly spaced contour lines surrounding GA lesions. Linear mixed models were applied to assess the association between photoreceptor-related imaging features and GA progression rates and characterize the pattern of photoreceptor degeneration over time.Association of ONL thinning with follow-up time (after adjusting for age, retinal topography [z score], and distance to the GA boundary).The study included 158 eyes of 89 patients (51 women and 38 men) with a mean (SD) age of 77.7 (7.1) years. The fully automated B-scan segmentation was accurate (dice coefficient, 0.82; 95% CI, 0.80-0.85; compared with manual markings) and revealed a marked interpatient variability in photoreceptor degeneration. The ellipsoid zone (EZ) loss-to-GA boundary distance and OS thickness were prognostic for future progression rates. Outer nuclear layer and IS thinning over time was significant even when adjusting for age and proximity to the GA boundary (estimates of -0.16 μm/y; 95% CI, -0.30 to -0.02; and -0.17 μm/y; 95% CI, -0.26 to -0.09).Distinct and progressive alterations of photoreceptor laminae (exceeding GA spatially) were detectable and quantifiable. The degree of photoreceptor degeneration outside of regions of retinal pigment epithelium atrophy varied markedly between eyes and was associated with future GA progression. Macula-wide photoreceptor laminae thinning represents a potential candidate end point to monitor treatment effects beyond mere GA lesion size progression.

  View details for DOI 10.1001/jamaophthalmol.2020.2914

  View details for PubMedID 32789526

• Complete RPE and outer retinal atrophy in patients receiving anti-VEGF treatment for neovascular age-related macular degeneration. PloS one Eng, V. A., Rayess, N., Nguyen, H. V., Leng, T. 2020; 15 (5): e0232353

  Abstract

  IMPORTANCE: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness with several intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents available for its management such as aflibercept, bevacizumab, and ranibizumab. However, direct comparisons between these three agents among the same patient population are limited.OBJECTIVE: To assess the rate and growth of complete retinal pigment epithelium and outer retinal atrophy (cRORA) in eyes with nAMD treated with aflibercept, bevacizumab, and/or ranibizumab.METHOD: Retrospective cohort study of patients with treatment-naive neovascular AMD seen at an academic hospital between October 2006 and February 2019. Study eyes were treated with intravitreal injections of aflibercept, bevacizumab, and/or ranibizumab and followed for two years.MAIN OUTCOMES AND MEASURES: cRORA prevalence, location, size, and growth rate. Eyes were imaged with Cirrus spectral domain optical coherence tomography (SD-OCT). Presence and size of cRORA were calculated using the FDA-approved Advanced RPE Analysis software. Linear regression models were used to correlate cRORA progression with baseline demographic and ocular characteristics, anti-VEGF drug, and number of injections. Unpaired t-tests, ANOVA, and linear regression models were computed with SAS 9.4.RESULTS: 197 eyes from 158 patients (mean age 78.9, 62.9% women) received an average of 13 anti-VEGF injections over 24 months. 22% developed new cRORA. Mean cRORA area increased from 1.71 mm2 to 2.93 mm2. At 24 months, eyes with 11+ injections had significantly less cRORA area (11+ injections, 4.02 mm2; ≤ 10 injections, 2.46 mm2; p = 0.01) and growth rate (11+ injections, 0.41 mm2/year; ≤ 10 injections, 1.05 mm2/year; p = 0.02). Choice of anti-VEGF drug yielded no significant difference in cRORA progression.CONCLUSIONS AND RELEVANCE: Treating nAMD with aflibercept, bevacizumab or ranibizumab demonstrated comparable cRORA development at 24 months. Number of injections inversely correlated with cRORA area and growth. These results warrant further investigation in the pathophysiology of cRORA in anti-VEGF treated eyes.

  View details for DOI 10.1371/journal.pone.0232353

  View details for PubMedID 32369500

• Reductions in final visual acuity occur even within the first 3 days after a macula-off retinal detachment BRITISH JOURNAL OF OPHTHALMOLOGY Greven, M. A., Leng, T., Silva, R., Leung, L., Karth, P. A., Moshfeghi, D. M., Sanislo, S. R., Schachar, I. H. 2019; 103 (10): 161–64

  View details for DOI 10.1136/bjophthalmol-2018-313191

  View details for Web of Science ID 000505163800027

• Reply to Letter to the Editor: Preventing Progression in Nonexudative Age-Related Macular Degeneration With Subthreshold Laser Therapy: A Systematic Review OPHTHALMIC SURGERY LASERS & IMAGING RETINA Eng, V. A., Leng, T. 2019; 50 (9): 602–3

  View details for Web of Science ID 000489323500019

• Imaging, Genetic, and Demographic Factors Associated With Conversion to Neovascular Age-Related Macular Degeneration: Secondary Analysis of a Randomized Clinical Trial JAMA OPHTHALMOLOGY Hallak, J. A., de Sisternes, L., Osborne, A., Yaspan, B., Rubin, D. L., Leng, T. 2019; 137 (7): 738–44

  View details for DOI 10.1001/jamaophthalmol.2019.0868

  View details for Web of Science ID 000481513900003

• Reflectance adaptive optics scanning light ophthalmoscopy of epiretinal membranes Razeen, M. M., Leng, T., Dubra, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488628104378

• A Comparison: Structural optical coherence tomography and angiography in diabetic retinopathy and diabetic macular edema Huang, L. C., Shariati, A., Oh, A., Leng, T., Liao, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488628107153

• Regression patterns of Retinopathy of Prematurity after intravitreal injection of Ranibizumab Ji, M. H., Moshfeghi, D., Shields, R. A., Bodnar, Z., Ludwig, C. A., Callaway, N. F., Leng, T., Sanislo, S., Orazi, L., Amorelli, G., Lepore, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488800707257

• Preventing Progression in Nonexudative Age-Related Macular Degeneration With Subthreshold Laser Therapy: A Systematic Review OPHTHALMIC SURGERY LASERS & IMAGING RETINA Eng, V. A., Wood, E. H., Boddu, S., Karth, P. A., Leng, T. 2019; 50 (3): E61–E70

  Abstract

  Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly in developed countries. Subthreshold retinal laser therapy is a new technique that targets drusen - a marker of nonexudative AMD - without causing incidental retinal damage associated with conventional laser photocoagulation. This review summarizes published literature on subthreshold retinal laser therapy as prophylactic treatment of nonexudative AMD.A literature search of the PubMed, Medline, and Embase databases was conducted from January 1997 to April 2018. Studies were analyzed based upon study design, laser parameters, drusen reduction, changes in visual acuity (VA), and the development of choroidal neovascularization (CNV) and/or geographic atrophy (GA).Twelve studies involving 2,481 eyes treated with subthreshold retinal laser therapy were included in this review. Treatment led to increased drusen reduction, and studies with significant VA improvement were associated with significant drusen reduction. There was no significant change in the risk of developing CNV or GA.Subthreshold retinal laser therapy is effective for reducing drusen and potentially improving vision in patients with nonexudative AMD. This therapy does not show benefits in reducing development of CNV or GA. Thus, its long-term efficacy to prevent progression to advanced AMD cannot yet be recommended. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e61-e70.].

  View details for DOI 10.3928/23258160-20190301-13

  View details for Web of Science ID 000462056800003

  View details for PubMedID 30893458

• Geographic atrophy segmentation in SD-OCT images using synthesized fundus autofluorescence imaging. Computer methods and programs in biomedicine Wu, M. n., Cai, X. n., Chen, Q. n., Ji, Z. n., Niu, S. n., Leng, T. n., Rubin, D. L., Park, H. n. 2019; 182: 105101

  Abstract

  Accurate assessment of geographic atrophy (GA) is critical for diagnosis and therapy of non-exudative age-related macular degeneration (AMD). Herein, we propose a novel GA segmentation framework for spectral-domain optical coherence tomography (SD-OCT) images that employs synthesized fundus autofluorescence (FAF) images.An en-face OCT image is created via the restricted sub-volume projection of three-dimensional OCT data. A GA region-aware conditional generative adversarial network is employed to generate a plausible FAF image from the en-face OCT image. The network balances the consistency between the entire synthesize FAF image and the lesion. We use a fully convolutional deep network architecture to segment the GA region using the multimodal images, where the features of the en-face OCT and synthesized FAF images are fused on the front-end of the network.Experimental results for 56 SD-OCT scans with GA indicate that our synthesis algorithm can generate high-quality synthesized FAF images and that the proposed segmentation network achieves a dice similarity coefficient, an overlap ratio, and an absolute area difference of 87.2%, 77.9%, and 11.0%, respectively.We report an automatic GA segmentation method utilizing synthesized FAF images.Our method is effective for multimodal segmentation of the GA region and can improve AMD treatment.

  View details for DOI 10.1016/j.cmpb.2019.105101

  View details for PubMedID 31600644

• A MULTI-SCALE DEEP CONVOLUTIONAL NEURAL NETWORK FOR JOINT SEGMENTATION AND PREDICTION OF GEOGRAPHIC ATROPHY IN SD-OCT IMAGES Zhang, Y., Ji, Z., Niu, S., Leng, T., Rubin, D. L., Chen, Q., IEEE IEEE. 2019: 565–68

  View details for Web of Science ID 000485040000125

• Automatically Determining the Confocal Parameters From OCT B-Scans for Quantification of the Attenuation Coefficients IEEE TRANSACTIONS ON MEDICAL IMAGING Dwork, N., Smith, G. T., Leng, T., Pauly, J. M., Bowden, A. K. 2019; 38 (1): 261–68

  Abstract

  The attenuation coefficient is a relevant biomarker for many diagnostic medical applications. Recently, the Depth-Resolved Confocal (DRC) technique was developed to automatically estimate the attenuation coefficients from Optical Coherence Tomography (OCT) data with pixel-level resolution. However, DRC requires that the confocal function parameters (i.e., focal plane location and apparent Rayleigh range) be known a priori. In this paper, we present the autoConfocal algorithm: a simple, automatic method for estimating those parameters directly from OCT imagery when the focal plane is within the sample. We present autoConfocal+DRC results on phantom data, ex-vivo biological tissue data, and in-vivo clinical data.

  View details for DOI 10.1109/TMI.2018.2861570

  View details for Web of Science ID 000455110500025

  View details for PubMedID 30072317

• Thomas A. Swift's Electric Rifle Injuries to the Eye and Ocular Adnexa: The Management of Complex Trauma. Ophthalmology. Retina Moysidis, S. N., Koulisis, N. n., Rodger, D. C., Chao, J. R., Leng, T. n., de Carlo, T. n., Burkemper, B. n., Ediriwickrema, L. S., George, M. S., Jiang, Y. n., Bohm, K. J., Gulati, S. n., Torres, R. J., Meallet, M. A., Moshfeghi, A. A., Flynn, H. W., Mieler, W. F., Williams, G. A., Humayun, M. S., Eliott, D. n. 2019; 3 (3): 258–69

  Abstract

  To report the ocular and adnexal injuries sustained by patients with Thomas A. Swift's electric rifles (TASER; TASER International, Scottsdale, AZ), review the literature, and discuss the management of this complex trauma.Multicenter, retrospective case series and literature review.Seventeen eyes of 16 patients (5 eyes of 5 patients treated at 3 institutions, and 12 eyes of 11 previously reported cases).The clinical data of 17 eyes were pooled. Spearman's correlation coefficient was used to assess the association between the extent of TASER injury and patient outcomes.Extent of TASER injury (zone of injury, penetrating vs. perforating) and association with patient outcomes (visual acuity [VA] and retinal detachment [RD]).In our cohort, 4 patients were transported by law enforcement and 1 was transferred from a community hospital. Four patients were taken to the operating room for TASER removal and globe repair; 1 patient underwent removal in the emergency room. Of 17 pooled cases, 12 (71%) involved open-globe injury. Of these, there was a high rate of zone 3 injuries (100%; n = 12) and a high incidence of RD (73%; 8 of 11, eviscerated eye excluded). Among patients with closed-globe injury (n = 5), 1 patient demonstrated exudative RD and 1 patient demonstrated retinal dialysis with RD. Of 10 patients with RD, 1 (10%) achieved resolution with monitoring (exudative RD); 1 (10%) underwent cryopexy and pneumatic retinopexy; 3 (30%) underwent vitrectomy, and 5 (50%) with poor prognosis did not undergo vitreoretinal surgery. In the 3 patients who underwent vitrectomy, all 3 (100%) demonstrated redetachment resulting from proliferative vitreoretinopathy and required additional surgery. Visual acuity on presentation was significantly correlated with final VA (ρ = 0.783; P = 0.02). Men (94%) were more likely than women (6%) to sustain TASER trauma. Median age was 26 years. There was a 50% rate of loss to follow-up.Thomas A. Swift's electric rifle injuries to the eyes or ocular adnexa represent complex trauma. Zone 3 injuries are common. The visual prognosis is guarded, and eyes may require multiple surgeries to preserve vision. Patients are at high risk for loss to follow-up by way of incarceration.

  View details for PubMedID 31014704

• Reductions in final visual acuity occur even within the first 3 days after a macula-off retinal detachment. The British journal of ophthalmology Greven, M. A., Leng, T., Silva, R. A., Leung, L. B., Karth, P. A., Moshfeghi, D. M., Sanislo, S. R., Schachar, I. H. 2018

  Abstract

  PURPOSE: To determine if final visual acuity (VA) is affected by duration of macular detachment (DMD) within the first week of macula-off retinal detachment (RD).METHODS: This is a retrospective study of eyes that underwent repair within 7 days with vitrectomy or vitrectomy with scleral buckle for macula-off RD at Stanford University Hospital between 1 May 2007 and 1 May 2017. A generalised linear model was constructed using DMD, postoperative lens status, preoperative VA, patient age and surgeon as the independent variables and the final VA as the dependent variable. The main outcome measure was the final VA.RESULTS: Seventy-nine eyes met the entry criteria. Group 1 included 52 eyes with RD repaired within 3 days of DMD, and group 2 included 27 eyes repaired between 4 and 7 days of DMD. The average final VA in group 1 eyes was logarithm of the minimum angle of resolution (logMAR) 0.21 (Snellen 20/33) and in group 2 eyes was logMAR 0.54 (Snellen 20/69). In group 1 and group 2 eyes, preoperative VA (p=0.017and p=0.007), DMD (p=0.004 and p=0.041) and final lens status (p<0.0001and p<0.001) predicted postoperative VA. Post-hoc analysis showed significant differences in final VA between detachments of 1day vs 3 days (p=0.0009).CONCLUSION: DMD affects the final VA even among patients whose DMD is <3 days. Based on these results, interventions that shorten DMD, including those occurring within the first 3days, may result in improved long-term VA outcomes.

  View details for PubMedID 30504489

• Progressive Reductions in Acuity Occur even within the First Three Days After a Macula-Off Retinal Detachment Greven, M., Leng, T., Leung, L., Moshfeghi, D. M., Sanislo, S., Silva, R., Schachar, I. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912503092

• Micro-RNAs in the pathogenesis of epiretinal membrane (ERM) formation Kaidonis, G., Stary, C. M., Leng, T. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442932805293

• Automatic identification of referral-warranted diabetic retinopathy using deep learning on mobile phone images Leng, T., Greven, M., Smith, S., Ludwig, C., Chang, R., Gargeya, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912505027

• Beyond Retinal Layers: A Deep Voting Model for Automated Geographic Atrophy Segmentation in SD-OCT Images TRANSLATIONAL VISION SCIENCE & TECHNOLOGY Ji, Z., Chen, Q., Niu, S., Leng, T., Rubin, D. L. 2018; 7 (1): 1

  Abstract

  To automatically and accurately segment geographic atrophy (GA) in spectral-domain optical coherence tomography (SD-OCT) images by constructing a voting system with deep neural networks without the use of retinal layer segmentation.An automatic GA segmentation method for SD-OCT images based on the deep network was constructed. The structure of the deep network was composed of five layers, including one input layer, three hidden layers, and one output layer. During the training phase, the labeled A-scans with 1024 features were directly fed into the network as the input layer to obtain the deep representations. Then a soft-max classifier was trained to determine the label of each individual pixel. Finally, a voting decision strategy was used to refine the segmentation results among 10 trained models.Two image data sets with GA were used to evaluate the model. For the first dataset, our algorithm obtained a mean overlap ratio (OR) 86.94% ± 8.75%, absolute area difference (AAD) 11.49% ± 11.50%, and correlation coefficients (CC) 0.9857; for the second dataset, the mean OR, AAD, and CC of the proposed method were 81.66% ± 10.93%, 8.30% ± 9.09%, and 0.9952, respectively. The proposed algorithm was capable of improving over 5% and 10% segmentation accuracy, respectively, when compared with several state-of-the-art algorithms on two data sets.Without retinal layer segmentation, the proposed algorithm could produce higher segmentation accuracy and was more stable when compared with state-of-the-art methods that relied on retinal layer segmentation results. Our model may provide reliable GA segmentations from SD-OCT images and be useful in the clinical diagnosis of advanced nonexudative AMD.Based on the deep neural networks, this study presents an accurate GA segmentation method for SD-OCT images without using any retinal layer segmentation results, and may contribute to improved understanding of advanced nonexudative AMD.

  View details for PubMedID 29302382

• Automated detection of foveal center in SD-OCT images using the saliency of retinal thickness maps MEDICAL PHYSICS Niu, S., Chen, Q., de Sisternes, L., Leng, T., Rubin, D. L. 2017; 44 (12): 6390–6403

  View details for DOI 10.1002/mp.12614

  View details for Web of Science ID 000425379200027

• Automated detection of foveal center in SD-OCT images using the saliency of retinal thickness maps. Medical physics Niu, S., Chen, Q., de Sisternes, L., Leng, T., Rubin, D. L. 2017; 44 (12): 6390-6403

  Abstract

  To develop an automated method based on saliency map of the retinal thickness map to determine foveal center in spectral-domain optical coherence tomography (SD-OCT) images.This paper proposes an automatic method for the detection of the foveal center in SD-OCT images. Initially, a retinal thickness map is generated by considering the axial distance between the internal limiting membrane (ILM) and the Bruch's membrane (BM). Both the ILM and BM boundaries are automatically segmented by a known retinal segmentation technique. The macular foveal region is identified as a salient feature in the retinal thickness map, and segmented by the saliency detection method based on a human vision attention model. Finally, the foveal center is identified by searching for the lowest point from the determined macular fovea region.Experimental results in 39 scans from 35 healthy eyes and 58 scans from 29 eyes diagnosed with several stages of age-related macular degeneration (AMD), from mild or intermediate stages to severe dry or wet stages, demonstrated that the proposed method achieves good performance. The mean radial distance error of the automatically detected foveal center locations when compared to consensus manual determination established by repeated sessions from two expert readers was 52 ± 56 μm for the normal eyes and 73 ± 63 μm for AMD eyes.The proposed algorithm was more effective for detecting the foveal center automatically in SD-OCT images than the state-of-art methods.

  View details for DOI 10.1002/mp.12614

  View details for PubMedID 28976639

• Valved 25-Gauge Cannula for Vitreous Tap and Injection OPHTHALMIC SURGERY LASERS & IMAGING RETINA Leng, T., Moshfeghi, D. M. 2017; 48 (11): 916–17

  Abstract

  To describe a technique that reduces patient discomfort by using a valved 25-gauge trocar for vitreous tap and intravitreal injection of medications in previously vitrectomized eyes with suspected infectious endophthalmitis.A commercially available 25-gauge valved entry system is used to enter the vitreous cavity. A 25-gauge needle attached to a syringe is used to obtain a vitreous specimen for microbiological access and administer intravitreal injections of antibiotics and steroids. No vitreous volume is lost during these procedures because of the cannula's valve. At the completion of the tap and injections, the cannula is removed with forceps and the single wound tamponaded with a cotton-tipped applicator.With this method, a vitreous tap and injection of pharmacologic agents only requires one piercing through the sclera, instead of the usual four piercings.With this new technique, it is possible to enhance patient comfort, decreased pain, and reduce trauma to the conjunctiva. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:916-917.].

  View details for DOI 10.3928/23258160-20171030-07

  View details for Web of Science ID 000418012200007

  View details for PubMedID 29121361

• En Face Optical Coherence Tomography Angiography Imaging Versus Fundus Photography in the Measurement of Choroidal Nevi OPHTHALMIC SURGERY LASERS & IMAGING RETINA Lee, M. D., Kaidonis, G., Kim, A. Y., Shields, R. A., Leng, T. 2017; 48 (9): 741–47

  Abstract

  Choroidal nevi are common benign intraocular tumors with a small risk of malignant transformation. This retrospective study investigates the use of en face spectral-domain optical coherence tomography angiography (SD-OCTA) in determining the clinical features and measurement of choroidal nevi.Patients with choroidal nevi were imaged with both OCTA and a fundus photography device. Greatest longitudinal dimension (GLD), perpendicular dimension (PD), and the GLD/PD ratio were assessed on each device. Inter-device variation and intra- and inter-rater reliability analyses were performed.Fourteen patients with choroidal nevi were included. No significant difference between the GLD/PD ratio as measured by all three devices was found (Chi-square = 2.8, 2 df, P = .247). Intraclass correlation coefficients were greater than 0.7 for repeated measures on all devices, suggesting good repeatability and reproducibility.This study demonstrated inter-device consistency and high intra- and inter-rater reliability when measuring choroidal nevi. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:741-747.].

  View details for DOI 10.3928/23258160-20170829-09

  View details for Web of Science ID 000416072300008

  View details for PubMedID 28902335

• The superficial and deep retinal capillary plexus in cases of fovea plana imaged by spectral-domain optical coherence tomography angiography. American journal of ophthalmology case reports Kaidonis, G., Silva, R. A., Sanislo, S. R., Leng, T. 2017; 6: 41–44

  Abstract

  Purpose: To describe the appearance of the superficial and deep retinal capillary plexi in three patients with fovea plana of differing severity using spectral-domain optical coherence tomography angiography (OCTA).Observations: In the first case of grade 1 fovea plana (a patient with 20/25 vision), OCTA showed an orderly branching pattern of vessels from the superficial and deep retinal plexi extending to the center of the fovea. The second case of grade 3 fovea plana (20/30 vision) showed some disruption of the orderly vascular pattern with small caliber vessels from both superficial and deep layers densely covering the fovea center. Case 3 represented a patient with grade 4 fovea plana associated with PAX6 mutation and poor visual acuity. OCTA revealed a disorganized pattern of large and small caliber vessels from the superficial capillary network extending into the center of the fovea.Conclusions and importance: Previously available imaging modalities were unable to specifically target different layers of the retinal vasculature. Using OCTA we have been able to show progressive changes in the vascular pattern in the deep and superficial retinal layers of patients with different grades of fovea plana. This novel imaging technique may play a role in the classification and assessment of patients with fovea plana.

  View details for PubMedID 29260054

• Manual Removal of Intraocular Lens Silicone Oil Droplets and Dystrophic Calcifications Using a Nitinol Loop: A Case Series. Ophthalmic surgery, lasers & imaging retina Moussa, K., Leng, T., Oatts, J. T., Bhisitkul, R. B., Hwang, D. G., Stewart, J. M. 2017; 48 (5): 422-426

  Abstract

  Deposition of dystrophic calcifications on the posterior surface of silicone intraocular lenses (IOLs) has been reported in patients with asteroid hyalosis. Accumulation of silicone oil droplets on the posterior surface of silicone IOLs in silicone-filled eyes has also been reported. Recently, a novel technique to manually remove dystrophic calcifications using a nickel titanium loop (Finesse Flex Loop; Alcon, Fort Worth, TX) was described, obviating the need for IOL exchange. Here, the authors report their outcomes with this technique in five eyes with IOL dystrophic calcifications as well as one eye with IOL silicone oil droplet accumulation. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:422-426.].

  View details for DOI 10.3928/23258160-20170428-09

  View details for PubMedID 28499054

• Automated Identification of Diabetic Retinopathy Using Deep Learning. Ophthalmology Gargeya, R., Leng, T. 2017

  Abstract

  Diabetic retinopathy (DR) is one of the leading causes of preventable blindness globally. Performing retinal screening examinations on all diabetic patients is an unmet need, and there are many undiagnosed and untreated cases of DR. The objective of this study was to develop robust diagnostic technology to automate DR screening. Referral of eyes with DR to an ophthalmologist for further evaluation and treatment would aid in reducing the rate of vision loss, enabling timely and accurate diagnoses.We developed and evaluated a data-driven deep learning algorithm as a novel diagnostic tool for automated DR detection. The algorithm processed color fundus images and classified them as healthy (no retinopathy) or having DR, identifying relevant cases for medical referral.A total of 75 137 publicly available fundus images from diabetic patients were used to train and test an artificial intelligence model to differentiate healthy fundi from those with DR. A panel of retinal specialists determined the ground truth for our data set before experimentation. We also tested our model using the public MESSIDOR 2 and E-Ophtha databases for external validation. Information learned in our automated method was visualized readily through an automatically generated abnormality heatmap, highlighting subregions within each input fundus image for further clinical review.We used area under the receiver operating characteristic curve (AUC) as a metric to measure the precision-recall trade-off of our algorithm, reporting associated sensitivity and specificity metrics on the receiver operating characteristic curve.Our model achieved a 0.97 AUC with a 94% and 98% sensitivity and specificity, respectively, on 5-fold cross-validation using our local data set. Testing against the independent MESSIDOR 2 and E-Ophtha databases achieved a 0.94 and 0.95 AUC score, respectively.A fully data-driven artificial intelligence-based grading algorithm can be used to screen fundus photographs obtained from diabetic patients and to identify, with high reliability, which cases should be referred to an ophthalmologist for further evaluation and treatment. The implementation of such an algorithm on a global basis could reduce drastically the rate of vision loss attributed to DR.

  View details for DOI 10.1016/j.ophtha.2017.02.008

  View details for PubMedID 28359545

• Automated intraretinal segmentation of SD-OCT images in normal and age-related macular degeneration eyes BIOMEDICAL OPTICS EXPRESS de Sisternes, L., Jonna, G., Moss, J., Marmor, M. F., Leng, T., Rubin, D. L. 2017; 8 (3): 1926-1949

  Abstract

  This work introduces and evaluates an automated intra-retinal segmentation method for spectral-domain optical coherence (SD-OCT) retinal images. While quantitative assessment of retinal features in SD-OCT data is important, manual segmentation is extremely time-consuming and subjective. We address challenges that have hindered prior automated methods, including poor performance with diseased retinas relative to healthy retinas, and data smoothing that obscures image features such as small retinal drusen. Our novel segmentation approach is based on the iterative adaptation of a weighted median process, wherein a three-dimensional weighting function is defined according to image intensity and gradient properties, and a set of smoothness constraints and pre-defined rules are considered. We compared the segmentation results for 9 segmented outlines associated with intra-retinal boundaries to those drawn by hand by two retinal specialists and to those produced by an independent state-of-the-art automated software tool in a set of 42 clinical images (from 14 patients). These images were obtained with a Zeiss Cirrus SD-OCT system, including healthy, early or intermediate AMD, and advanced AMD eyes. As a qualitative evaluation of accuracy, a highly experienced third independent reader blindly rated the quality of the outlines produced by each method. The accuracy and image detail of our method was superior in healthy and early or intermediate AMD eyes (98.15% and 97.78% of results not needing substantial editing) to the automated method we compared against. While the performance was not as good in advanced AMD (68.89%), it was still better than the manual outlines or the comparison method (which failed in such cases). We also tested our method's performance on images acquired with a different SD-OCT manufacturer, collected from a large publicly available data set (114 healthy and 255 AMD eyes), and compared the data quantitatively to reference standard markings of the internal limiting membrane and inner boundary of retinal pigment epithelium, producing a mean unsigned positioning error of 6.04 ± 7.83µm (mean under 2 pixels). Our automated method should be applicable to data from different OCT manufacturers and offers detailed layer segmentations in healthy and AMD eyes.

  View details for DOI 10.1364/BOE.8.001926

  View details for Web of Science ID 000395942600047

  View details for PubMedCentralID PMC5480589

• Automated intraretinal segmentation of SD-OCT images in normal and age-related macular degeneration eyes. Biomedical optics express de Sisternes, L., Jonna, G., Moss, J., Marmor, M. F., Leng, T., Rubin, D. L. 2017; 8 (3): 1926-1949

  Abstract

  This work introduces and evaluates an automated intra-retinal segmentation method for spectral-domain optical coherence (SD-OCT) retinal images. While quantitative assessment of retinal features in SD-OCT data is important, manual segmentation is extremely time-consuming and subjective. We address challenges that have hindered prior automated methods, including poor performance with diseased retinas relative to healthy retinas, and data smoothing that obscures image features such as small retinal drusen. Our novel segmentation approach is based on the iterative adaptation of a weighted median process, wherein a three-dimensional weighting function is defined according to image intensity and gradient properties, and a set of smoothness constraints and pre-defined rules are considered. We compared the segmentation results for 9 segmented outlines associated with intra-retinal boundaries to those drawn by hand by two retinal specialists and to those produced by an independent state-of-the-art automated software tool in a set of 42 clinical images (from 14 patients). These images were obtained with a Zeiss Cirrus SD-OCT system, including healthy, early or intermediate AMD, and advanced AMD eyes. As a qualitative evaluation of accuracy, a highly experienced third independent reader blindly rated the quality of the outlines produced by each method. The accuracy and image detail of our method was superior in healthy and early or intermediate AMD eyes (98.15% and 97.78% of results not needing substantial editing) to the automated method we compared against. While the performance was not as good in advanced AMD (68.89%), it was still better than the manual outlines or the comparison method (which failed in such cases). We also tested our method's performance on images acquired with a different SD-OCT manufacturer, collected from a large publicly available data set (114 healthy and 255 AMD eyes), and compared the data quantitatively to reference standard markings of the internal limiting membrane and inner boundary of retinal pigment epithelium, producing a mean unsigned positioning error of 6.04 ± 7.83µm (mean under 2 pixels). Our automated method should be applicable to data from different OCT manufacturers and offers detailed layer segmentations in healthy and AMD eyes.

  View details for DOI 10.1364/BOE.8.001926

  View details for PubMedID 28663874

  View details for PubMedCentralID PMC5480589

• Spectral Domain Optical Coherence Tomography Angiography in Stargardt's Macular Dystrophy. Ophthalmology. Retina Lee, M., Kaidonis, G., Leng, T. 2017; 1 (5): 452-454

  View details for DOI 10.1016/j.oret.2016.12.008

  View details for PubMedID 31047578

• Individual Drusen Segmentation and Repeatability and Reproducibility of Their Automated Quantification in Optical Coherence Tomography Images. Translational vision science & technology de Sisternes, L., Jonna, G., Greven, M. A., Chen, Q., Leng, T., Rubin, D. L. 2017; 6 (1): 12-?

  Abstract

  To introduce a novel method to segment individual drusen in spectral-domain optical coherence tomography (SD-OCT), and evaluate its accuracy, and repeatability/reproducibility of drusen quantifications extracted from the segmentation results.Our method uses a smooth interpolation of the retinal pigment epithelium (RPE) outer boundary, fitted to candidate locations in proximity to Bruch's Membrane, to identify regions of substantial lifting in the inner-RPE or inner-segment boundaries, and then separates and evaluates individual druse independently. The study included 192 eyes from 129 patients. Accuracy of drusen segmentations was evaluated measuring the overlap ratio (OR) with manual markings, also comparing the results to a previously proposed method. Repeatability and reproducibility across scanning protocols of automated drusen quantifications were investigated in repeated SD-OCT volume pairs and compared with those measured by a commercial tool (Cirrus HD-OCT).Our segmentation method produced higher accuracy than a previously proposed method, showing similar differences to manual markings (0.72 ± 0.09 OR) as the measured intra- and interreader variability (0.78 ± 0.09 and 0.77 ± 0.09, respectively). The automated quantifications displayed high repeatability and reproducibility, showing a more stable behavior across scanning protocols in drusen area and volume measurements than the commercial software. Measurements of drusen slope and mean intensity showed significant differences across protocols.Automated drusen outlines produced by our method show promising accurate results that seem relatively stable in repeated scans using the same or different scanning protocols.The proposed method represents a viable tool to measure and track drusen measurements in early or intermediate age-related macular degeneration patients.

  View details for DOI 10.1167/tvst.6.1.12

  View details for PubMedID 28275527

  View details for PubMedCentralID PMC5338477

• Significant Bilateral Response in Diabetic Macular Edema After Single Unilateral Intravitreal Aflibercept Injection. Ophthalmic surgery, lasers & imaging retina Rahimy, E., Nyong'o, O., Leng, T. 2017; 48 (2): 167-169

  Abstract

  A 61-year-old patient with bilateral, treatment-naïve, diffuse diabetic macular edema (DME) that had been progressing during the previous 12 months received a single intravitreal injection of aflibercept (Eylea; Regeneron, Tarrytown, NY) to the left eye. At 2-week follow-up, noticeable bilateral improvement of the DME was observed by spectral-domain optical coherence tomography imaging with commensurate improvement of visual acuity to 20/30 bilaterally. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:167-169.].

  View details for DOI 10.3928/23258160-20170130-11

  View details for PubMedID 28195620

• Retinotomy Closure Following Subretinal Stem Cell Transplant With a 30-Gauge Needle. Ophthalmic surgery, lasers & imaging retina Ludwig, C. A., Leng, T. 2016; 47 (9): 869-873

  Abstract

  The authors report two cases of posterior retinotomy closure following subretinal stem cell transplantation for age-related macular degeneration with a 30-gauge needle - a larger bore needle than those used in prior studies. Partial retinotomy closure was seen on optical coherence tomography within 24 hours in one patient, whereas complete closure occurred by the 5-month and 1-year follow-up visits. A trace retinal hemorrhage occurred in one case, with resolution by 12 weeks. These findings demonstrate the likelihood of uncomplicated, spontaneous retinotomy closure following subretinal stem cell transplantation with a 30-gauge needle. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:869-873.].

  View details for DOI 10.3928/23258160-20160901-12

  View details for PubMedID 27631485

• Fully Automated Prediction of Geographic Atrophy Growth Using Quantitative Spectral-Domain Optical Coherence Tomography Biomarkers. Ophthalmology Niu, S., de Sisternes, L., Chen, Q., Rubin, D. L., Leng, T. 2016; 123 (8): 1737-1750

  Abstract

  To develop a predictive model based on quantitative characteristics of geographic atrophy (GA) to estimate future potential regions of GA growth.Progression study and predictive model.One hundred eighteen spectral-domain (SD) optical coherence tomography (OCT) scans of 38 eyes in 29 patients.Imaging features of GA quantifying its extent and location, as well as characteristics at each topographic location related to individual retinal layer thickness and reflectivity, the presence of pathologic features (like reticular pseudodrusen or loss of photoreceptors), and other known risk factors of GA growth, were extracted automatically from 118 SD OCT scans of 38 eyes from 29 patients collected over a median follow-up of 2.25 years. We developed and evaluated a model to predict the magnitude and location of GA growth at given future times using the quantitative features as predictors in 3 possible scenarios.Potential regions of GA growth.In descending order of out-of-bag feature importance, the most predictive SD OCT biomarkers for predicting the future regions of GA growth were thickness loss of bands 11 through 14 (5.66), reflectivity of bands 11 and 12 (5.37), thickness of reticular pseudodrusen (5.01), thickness of bands 5 through 11 (4.82), reflectivity of bands 7 through 11 (4.78), GA projection image (4.73), increased minimum retinal intensity map (4.59), and GA eccentricity (4.49). The predicted GA regions in the 3 tested scenarios resulted in a Dice index mean ± standard deviation of 0.81±0.12, 0.84±0.10, and 0.87±0.06, respectively, when compared with the observed ground truth. Considering only the regions without evidence of GA at baseline, predicted regions of future GA growth showed relatively high Dice indices of 0.72±0.18, 0.74±0.17, and 0.72±0.22, respectively. Predictions and actual values of GA growth rate and future GA involvement in the central fovea showed high correlations.Experimental results demonstrated the potential of our predictive model to predict future regions where GA is likely to grow and to identify the most discriminant early indicator (thickness loss of bands 11 through 14) of regions susceptible to GA growth.

  View details for DOI 10.1016/j.ophtha.2016.04.042

  View details for PubMedID 27262765

• En Face Imaging of Epiretinal Membranes and the Retinal Nerve Fiber Layer Using Swept-Source Optical Coherence Tomography. Ophthalmic surgery, lasers & imaging retina Greven, M. A., Elkin, Z., Nelson, R. W., Leng, T. 2016; 47 (8): 730-734

  Abstract

  To describe en face swept-source optical coherence tomography (SS-OCT) imaging of epiretinal membranes (ERMs) and the underlying retinal nerve fiber layer (RNFL).SS-OCT images were captured in nine eyes with ERMs. These SS-OCT en face images were qualitatively compared to spectral-domain OCT (SD-OCT) en face images. Using SS-OCT, en face images of the RNFL were obtained, if possible.En face SS-OCT images of ERMs were obtained in all nine eyes of eight individuals with clinically diagnosed ERMs that were superior to SD-OCT images. Clear en face images of the RNFL were acquired in seven of nine eyes (78%) using SS-OCT.SS-OCT is a novel method for generating en face images of ERMs. Compared with SDOCT en face images, SS-OCT could more clearly identify the plaques and folds of ERMs and underlying defects in the RNFL. Such images could be useful for surgical planning and assessment of the integrity of the underlying RNFL. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:730-734.].

  View details for DOI 10.3928/23258160-20160808-06

  View details for PubMedID 27548450

• 8 Questions with Dr. Moshfeghi. Ophthalmic surgery, lasers & imaging retina Leng, T., Moshfeghi, D. M. 2016; 47 (8): 786-788

  View details for DOI 10.3928/23258160-20160808-15

  View details for PubMedID 27548459

• PROSPECTIVE TRIAL OF ENDOGENOUS FUNGAL ENDOPHTHALMITIS AND CHORIORETINITIS RATES, CLINICAL COURSE, AND OUTCOMES IN PATIENTS WITH FUNGEMIA RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Paulus, Y. M., Cheng, S., Karth, P. A., Leng, T. 2016; 36 (7): 1357-1363

  Abstract

  Former studies have found rates of endogenous endophthalmitis ranging from 0% to 37% in patients with fungemia. This study sought to prospectively determine the rate and risk factors for endogenous chorioretinitis and endophthalmitis in patients with fungemia.A prospective cohort study was performed of consecutive adult inpatients at a single site from 2010 to 2013 of patients with positive blood cultures for fungus. One hundred and nineteen pieces of information were gathered for each patient.A total of 125 patients were enrolled in the study with 7 positive cases of chorioretinitis for a rate of 5.6%. Of these positive cases, 2 patients had endophthalmitis for a rate of 1.6%. Two patients who had a negative initial examination subsequently had a positive examination; 57% of the chorioretinitis patients who could report symptoms were asymptomatic, 57% of the chorioretinitis patients died, and 32% of negative cases died. Prolonged hospitalization, altered mental status, total parenteral nutrition, and gastrointestinal surgery were protective on univariate but not multivariate analysis.Despite modern antifungal therapy, fungal chorioretinitis and endophthalmitis continue to occur in patients with positive fungal cultures. Two dilated ophthalmic examinations should still be considered even in asymptomatic patients with fungemia.

  View details for DOI 10.1097/IAE.0000000000000919

  View details for Web of Science ID 000378595100036

  View details for PubMedID 26655621

• Spectral-Domain Optical Coherence Tomography Angiography of Central Retinal Artery Occlusion OPHTHALMIC SURGERY LASERS & IMAGING RETINA Damento, G., Chen, M. H., Leng, T. 2016; 47 (5): 467-470

  Abstract

  The authors report the use of optical coherence tomography angiography (OCTA) to determine retinal blood flow in a patient with central retinal artery occlusion (CRAO). Spectral-domain OCTA (SD-OCTA) was performed on an eye with CRAO. En face vascular images were constructed using an optical microangiography algorithm. The retinal vasculature was clearly imaged with high fidelity; areas of perfused retina were identified with exquisite detail. This study supports use of OCTA in diagnosing and monitoring CRAOs. Future research is warranted to recognize full potential of this imaging modality. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:467-470.].

  View details for DOI 10.3928/23258160-20160419-10

  View details for Web of Science ID 000378847000008

  View details for PubMedID 27183551

• Factors Associated With Poor Response to Aflibercept After Switching From Ranibizumab or Bevacizumab in Neovascular Age-related Macular Degeneration OPHTHALMIC SURGERY LASERS & IMAGING RETINA Cheng, S., Leng, T. 2016; 47 (5): 458-465

  Abstract

  The purpose of this study was to analyze demographic and ocular features of patients with age-related macular degeneration who failed aflibercept (Eylea; Regeneron, Tarrytown, NY) treatment after switching from ranibizumab (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech, South San Francisco, CA).Retrospective chart review of patients treated with aflibercept at the Byers Eye Institute from November 2011 to August 2014. Patient visual acuity was noted prior to aflibercept; after 1, 3, and 12 months; and on the most recent visit. Patients who improved vision after switching were compared to patients who lost vision. Demographic and imaging features were analyzed using univariate and multivariate statistics.Patients who lost vision had significantly higher BMI (P = .013, multivariate) and geographic atrophy (P = .0381, univariate; P = .1, multivariate) compared to patients who improved vision.BMI and geographic atrophy may be considered as potential indicators for poor response to aflibercept after switching from ranibizumab or bevacizumab. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:458-465.].

  View details for DOI 10.3928/23258160-20160419-09

  View details for Web of Science ID 000378847000007

  View details for PubMedID 27183550

• AFLIBERCEPT FOR THE TREATMENT OF RETINAL PIGMENT EPITHELIAL DETACHMENTS. Retina (Philadelphia, Pa.) He, L., Silva, R. A., Moshfeghi, D. M., Blumenkranz, M. S., Leng, T. 2016; 36 (3): 492-498

  Abstract

  To compare anatomical and visual acuity outcomes of eyes with persistent pigment epithelial detachments (PEDs) secondary to exudative age-related macular degeneration despite ranibizumab or bevacizumab treatment.After institutional review board approval, 40 eyes with PEDs switched from ranibizumab or bevacizumab to intravitreal aflibercept were compared for logMAR visual acuity, central subfield thickness on spectral domain optical coherence tomography, and PED height. Using paired t-tests, these parameters at baseline, after 3 consecutive injections, and 1 year after the switch were compared.Baseline visions of 20/61 ± 3.99 lines declined after 3 injections with aflibercept by 0.39 ± 2.43 lines (P = 0.32) and continued to fall after 1 year by 1.27 ± 3.48 lines (P = 0.03). Central subfield thickness was reduced after 3 injections (9.1 ± 52.0 μm, P = 0.27) and after 1 year (24.4 ± 55.3 μm, P = 0.01). The height of PEDs decreased by 31.7 ± 71.53 μm (P = 0.008) after 3 injections and by 47.81 ± 77.94 μm (P < 0.001) after 1 year.Switching to aflibercept from ranibizumab or bevacizumab resulted in a reduction in the height of PED and central subfield thickness, but a trend toward worse visual acuity 1 year after the switch.

  View details for DOI 10.1097/IAE.0000000000000749

  View details for PubMedID 26398694

• Mobile Health in the Retinal Clinic Population: Access to and Interest in Self-Tracking. Ophthalmic surgery, lasers & imaging retina Ludwig, C. A., Callaway, N. F., Park, J. H., Leng, T. 2016; 47 (3): 252-257

  Abstract

  Implementation of mobile health-tracking programs for retinal pathology requires both access to mobile devices and patient motivation to participate in self-tracking. The authors' study aimed to evaluate the prevalence of smartphone and tablet ownership and patient interest in self-tracking among a retinal clinic population.This is an institutional, prospective, cross-sectional survey of 103 retinal clinic outpatients. Consenting patients underwent a one-on-one interview conducted in the examination room during their waiting period by one researcher.Overall, 75 of 103 participants (72.2%) reported either owning a smartphone and/or tablet or having access at their household to a device that could be used to track eye health. The majority of participants (69 of 103 participants; 67%) reported interest in using a mobile application (smartphone or tablet) to track their eye health.These data suggest strong patient interest in the use of mobile devices to track eye health. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:252-257.].

  View details for DOI 10.3928/23258160-20160229-08

  View details for PubMedID 26985799

• Multi-Modal Longitudinal Evaluation of Subthreshold Laser Lesions in Human Retina, Including Scanning Laser Ophthalmoscope-Adaptive Optics Imaging. Ophthalmic surgery, lasers & imaging retina Wood, E. H., Leng, T., Schachar, I. H., Karth, P. A. 2016; 47 (3): 268-275

  Abstract

  Subthreshold retinal laser therapy is efficacious for a variety of retinovascular disorders. Currently, it is unknown which laser parameters can ensure no detectable damage to human retina tissue.One informed physician participant with a normal retina was treated with three levels (75%, 50%, and 25%) of subthreshold 577-nm laser (PASCAL; Topcon, Santa Clara, CA) at 20-millisecond (ms) duration and 100 µm spot size. Several high-resolution retinal imaging modalities, including spectral-domain optical coherence tomography (SD-OCT) and scanning laser ophthalmoscope-adaptive optics (SLO-AO), were used to longitudinally image retinal laser lesions during a 9-month period.SLO-AO and SD-OCT imaging of subthreshold laser therapy in human retina showed no cone cell or RPE damage at all time points during a 9-month period using the 25% threshold power 577-nm laser in the human retina.It is likely that subthreshold laser therapy with 577-nm laser at 20-ms duration in the human retina is safe at the 25% of threshold power level. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:268-275.].

  View details for DOI 10.3928/23258160-20160229-10

  View details for PubMedID 26985801

• Automated geographic atrophy segmentation for SD-OCT images using region-based C-V model via local similarity factor BIOMEDICAL OPTICS EXPRESS Niu, S., de Sisternes, L., Chen, Q., Leng, T., Rubin, D. L. 2016; 7 (2): 581-600

  Abstract

  Age-related macular degeneration (AMD) is the leading cause of blindness among elderly individuals. Geographic atrophy (GA) is a phenotypic manifestation of the advanced stages of non-exudative AMD. Determination of GA extent in SD-OCT scans allows the quantification of GA-related features, such as radius or area, which could be of important value to monitor AMD progression and possibly identify regions of future GA involvement. The purpose of this work is to develop an automated algorithm to segment GA regions in SD-OCT images. An en face GA fundus image is generated by averaging the axial intensity within an automatically detected sub-volume of the three dimensional SD-OCT data, where an initial coarse GA region is estimated by an iterative threshold segmentation method and an intensity profile set, and subsequently refined by a region-based Chan-Vese model with a local similarity factor. Two image data sets, consisting on 55 SD-OCT scans from twelve eyes in eight patients with GA and 56 SD-OCT scans from 56 eyes in 56 patients with GA, respectively, were utilized to quantitatively evaluate the automated segmentation algorithm. We compared results obtained by the proposed algorithm, manual segmentation by graders, a previously proposed method, and experimental commercial software. When compared to a manually determined gold standard, our algorithm presented a mean overlap ratio (OR) of 81.86% and 70% for the first and second data sets, respectively, while the previously proposed method OR was 72.60% and 65.88% for the first and second data sets, respectively, and the experimental commercial software OR was 62.40% for the second data set.

  View details for DOI 10.1364/BOE.7.000581

  View details for Web of Science ID 000369247000029

  View details for PubMedCentralID PMC4771473

• Improving Vitreoretinal Clinic Efficiency by Decentralizing Optical Coherence Tomography RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Callaway, N. F., Park, J. H., Maya-Silva, J., Leng, T. 2016; 36 (2): 335-341

  Abstract

  Patients in vitreoretinal clinic have long wait times that could be reduced by improving the efficiency of patient flow. The objective of this study was to determine whether decentralizing optical coherence tomography (OCT) into the technicians' room would reduce patient wait times and improve clinic efficiency.Randomized, single-center, clinical trial for 1 month without follow-up at Byers Eye Institute at Stanford. Subjects were return patients of three vitreoretinal specialists in March 2013. The intervention consisted of decentralizing OCT devices from the central photography suite into the technician screening rooms. Total clinic times and total wait times throughout subject appointments were recorded and compared with the control group (centralized photography suite). Secondary outcomes included frequency of injections, procedures, and primary diagnosis codes.Decentralized OCT reduced patient wait times by 74% and reduced total clinic appointment time by 36%. Subjects in the intervention arm experienced significantly reduced total wait time (mean difference = 15.9 minutes, P < 0.0001) and total time in clinic (mean difference = 22.9 minutes, P < 0.0001).Decentralized OCT represents the application of lean process concepts to improve vitreoretinal clinic efficiency. Decentralized OCT reduced both the total wait time and total time in clinic for return patients in a vitreoretinal clinic.

  View details for DOI 10.1097/IAE.0000000000000712

  View details for Web of Science ID 000369513500014

• THINKING LEAN: Improving Vitreoretinal Clinic Efficiency by Decentralizing Optical Coherence Tomography. Retina (Philadelphia, Pa.) Callaway, N. F., Park, J. H., Maya-Silva, J., Leng, T. 2016; 36 (2): 335-341

  Abstract

  Patients in vitreoretinal clinic have long wait times that could be reduced by improving the efficiency of patient flow. The objective of this study was to determine whether decentralizing optical coherence tomography (OCT) into the technicians' room would reduce patient wait times and improve clinic efficiency.Randomized, single-center, clinical trial for 1 month without follow-up at Byers Eye Institute at Stanford. Subjects were return patients of three vitreoretinal specialists in March 2013. The intervention consisted of decentralizing OCT devices from the central photography suite into the technician screening rooms. Total clinic times and total wait times throughout subject appointments were recorded and compared with the control group (centralized photography suite). Secondary outcomes included frequency of injections, procedures, and primary diagnosis codes.Decentralized OCT reduced patient wait times by 74% and reduced total clinic appointment time by 36%. Subjects in the intervention arm experienced significantly reduced total wait time (mean difference = 15.9 minutes, P < 0.0001) and total time in clinic (mean difference = 22.9 minutes, P < 0.0001).Decentralized OCT represents the application of lean process concepts to improve vitreoretinal clinic efficiency. Decentralized OCT reduced both the total wait time and total time in clinic for return patients in a vitreoretinal clinic.

  View details for DOI 10.1097/IAE.0000000000000712

  View details for PubMedID 26815931

• Automated geographic atrophy segmentation for SD-OCT images using region-based C-V model via local similarity factor. Biomedical optics express Niu, S., de Sisternes, L., Chen, Q., Leng, T., Rubin, D. L. 2016; 7 (2): 581-600

  Abstract

  Age-related macular degeneration (AMD) is the leading cause of blindness among elderly individuals. Geographic atrophy (GA) is a phenotypic manifestation of the advanced stages of non-exudative AMD. Determination of GA extent in SD-OCT scans allows the quantification of GA-related features, such as radius or area, which could be of important value to monitor AMD progression and possibly identify regions of future GA involvement. The purpose of this work is to develop an automated algorithm to segment GA regions in SD-OCT images. An en face GA fundus image is generated by averaging the axial intensity within an automatically detected sub-volume of the three dimensional SD-OCT data, where an initial coarse GA region is estimated by an iterative threshold segmentation method and an intensity profile set, and subsequently refined by a region-based Chan-Vese model with a local similarity factor. Two image data sets, consisting on 55 SD-OCT scans from twelve eyes in eight patients with GA and 56 SD-OCT scans from 56 eyes in 56 patients with GA, respectively, were utilized to quantitatively evaluate the automated segmentation algorithm. We compared results obtained by the proposed algorithm, manual segmentation by graders, a previously proposed method, and experimental commercial software. When compared to a manually determined gold standard, our algorithm presented a mean overlap ratio (OR) of 81.86% and 70% for the first and second data sets, respectively, while the previously proposed method OR was 72.60% and 65.88% for the first and second data sets, respectively, and the experimental commercial software OR was 62.40% for the second data set.

  View details for DOI 10.1364/BOE.7.000581

  View details for PubMedID 26977364

  View details for PubMedCentralID PMC4771473

• Noninvasive detection of microaneurysms in diabetic retinopathy by swept-source optical coherence tomography. Clinical ophthalmology (Auckland, N.Z.) Cheng, S., Leng, T. 2016; 10: 1791-1795

  Abstract

  A method of identifying retinal vascular microaneurysms (MAs) in nonproliferative diabetic retinopathy (NPDR) using swept-source optical coherence tomography (SS-OCT).SS-OCT images were acquired in 17 eyes with NPDR using prototype SS-OCT device and fluorescein angiography (FA) images were obtained simultaneously. MAs identified on SS-OCT slabs were correlated to MAs identified on FA.MAs were identified in SS-OCT slabs in 15/17 eyes, resulting in NPDR diagnosis rate of 88%. Mean number of MAs identified on FA was 11.7±11.9 (total 199) and was 8.1±9.3 (total 137) on SS-OCT. Wilcoxon rank sum test showed no significant difference in MAs detected on SS-OCT and FA (P=0.2995) across eyes. Wilcoxon rank sum test showed SS-OCT detected slightly fewer MAs than FA per eye (3.65 less, P=0.0009).SS-OCT visualization of MAs could serve as a tool for diagnosing NPDR, and possibly applied as an imaging biomarker for population-based diabetic retinopathy screening.

  View details for PubMedID 27695284

• Optical Coherence Tomography-Guided Short-Duration Positioning after Macular Hole Surgery. Ophthalmology. Retina Greven, M. A., Cheng, S. n., Leng, T. n. 2016; 1 (2): 176–78.e1

  View details for PubMedID 31047280

• Manual Removal of Dystrophic Calcifications From Silicone Intraocular Lenses Using a 27-Gauge Nitinol Loop With Concave Tines. Retina (Philadelphia, Pa.) Schachar, I., Leng, T. 2015; 35 (12): 2650-1

  View details for DOI 10.1097/IAE.0000000000000722

  View details for PubMedID 26274039

• Automated segmentation of optic disc in SD-OCT images and cup-to-disc ratios quantification by patch searching-based neural canal opening detection OPTICS EXPRESS Wu, M., Leng, T., de Sisternes, L., Rubin, D. L., Chen, Q. 2015; 23 (24): 31216-31229

  Abstract

  Glaucoma is one of the most common causes of blindness worldwide. Early detection of glaucoma is traditionally based on assessment of the cup-to-disc (C/D) ratio, an important indicator of structural changes to the optic nerve head. Here, we present an automated optic disc segmentation algorithm in 3-D spectral domain optical coherence tomography (SD-OCT) volumes to quantify this ratio. The proposed algorithm utilizes a two-stage strategy. First, it detects the neural canal opening (NCO) by finding the points with maximum curvature on the retinal pigment epithelium (RPE) boundary with a spatial correlation smoothness constraint on consecutive B-scans, and it approximately locates the coarse disc margin in the projection image using convex hull fitting. Then, a patch searching procedure using a probabilistic support vector machine (SVM) classifier finds the most likely patch with the NCO in its center in order to refine the segmentation result. Thus, a reference plane can be determined to calculate the C/D radio. Experimental results on 42 SD-OCT volumes from 17 glaucoma patients demonstrate that the proposed algorithm can achieve high segmentation accuracy and a low C/D ratio evaluation error. The unsigned border error for optic disc segmentation and the evaluation error for C/D ratio comparing with manual segmentation are 2.216 ± 1.406 pixels (0.067 ± 0.042 mm) and 0.045 ± 0.033, respectively.

  View details for DOI 10.1364/OE.23.031216

  View details for Web of Science ID 000366614100094

  View details for PubMedID 26698750

• Intraocular Nematode Affixed to Posterior Lens Capsule. Ophthalmic surgery, lasers & imaging retina Karth, P. A., Swinney, C. C., Moshfeghi, D. M., Yannuzzi, L. A., Pang, C. E., Leng, T. 2015; 46 (10): 1066-1067

  Abstract

  The clinical presentation of an intraocular nematode unusually affixed to the posterior lens capsule is described. A 64-year-old female patient presented with a 7-year history of gradually declining vision and enlarging central scotoma, but no inflammation. On follow-up 2 years later, vision had further declined and a non-motile, 8-mm nematode was seen affixed to the posterior lens capsule that remained unchanged through final follow-up. The patient disclosed having resided in Africa as a child. Systemic review revealed no evidence of extraocular involvement. Nematode carcasses may remain preserved in the human eye for extended periods without ongoing inflammation.

  View details for DOI 10.3928/23258160-20151027-16

  View details for PubMedID 26599254

• Short-Term Outcomes of Aflibercept Therapy for Diabetic Macular Edema in Patients With Incomplete Response to Ranibizumab and/or Bevacizumab. Ophthalmic surgery, lasers & imaging retina Wood, E. H., Karth, P. A., Moshfeghi, D. M., Leng, T. 2015; 46 (9): 950-954

  Abstract

  Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor recently approved by the U.S. Food and Drug Administration for the treatment of diabetic macular edema (DME). Currently, the effect of switching to aflibercept from other anti-VEGF agents for DME is unknown.In this prospective, interventional case series, DME patients with persistent retinal fluid despite regular (every 4 to 6 weeks) intravitreal injection (IVI) with ranibizumab 0.3 mg, and/or bevacizumab 1.25 mg were switched to IVI aflibercept 2 mg. Collected data included visual acuity, central subfield foveal thickness (CSFT), and the area of thickest edema on registered spectral-domain optical coherence tomography (SD-OCT).At 1 month after the first aflibercept IVI, 79% (11 of 14 eyes) showed anatomic improvement with a 23% decrease in average CSFT from 421 µm to 325 µm (P < .0132).A majority of patients with DME with persistent fluid on SD-OCT despite regular ranibizumab 0.3 mg and/or bevacizumab 1.25 mg IVIs showed a positive anatomic response to IVI aflibercept 2 mg. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:950-954.].

  View details for DOI 10.3928/23258160-20151008-08

  View details for PubMedID 26469235

• Restricted Summed-Area Projection for Geographic Atrophy Visualization in SD-OCT Images TRANSLATIONAL VISION SCIENCE & TECHNOLOGY Chen, Q., Niu, S., Shen, H., Leng, T., de Sisternes, L., Rubin, D. L. 2015; 4 (5)

  Abstract

  To enhance the rapid assessment of geographic atrophy (GA) across the macula in a single projection image generated from three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) scans by introducing a novel restricted summed-area projection (RSAP) technique.We describe a novel en face GA visualization technique, the RSAP, by restricting the axial projection of SD-OCT images to the regions beneath the Bruch's membrane (BM) boundary and also considering the choroidal vasculature's influence on GA visualization. The technique analyzes the intensity distribution beneath the retinal pigment epithelium (RPE) layer to fit a cross-sectional surface in the sub-RPE region. The area is taken as the primary GA projection. A median filter is then adopted to smooth the generated GA projection image. The RSAP technique was evaluated in 99 3D SD-OCT data sets from 27 eyes of 21 patients presenting with advanced nonexudative age-related macular degeneration and GA. We used the mean difference between GA and background regions and GA separability metric to measure GA contrast and distinction in the generated images, respectively. We compared our results with two existing GA projection techniques, the summed-voxel projection (SVP) and Sub-RPE Slab techniques.Comparative results demonstrate that the RSAP technique is more effective in displaying GA than the SVP and Sub-RPE Slab. The average of the mean difference between GA and background regions and the GA separability based on SVP, Sub-RPE Slab, and RSAP were 0.129/0.880, 0.238/0.919, and 0.276/0.938, respectively.The RSAP technique was more effective for GA visualization than the conventional SVP and Sub-RPE Slab techniques. Our technique decreases choroidal vasculature influence on GA projection images by analyzing the intensity distribution characteristics in sub-RPE regions. The generated GA projection image with the RSAP technique has improved contrast and distinction.Our method for automated generation of GA projection images from SD-OCT images may improve the visualization of the macular abnormalities and the management of GA.

  View details for DOI 10.1167/tvst.4.5.2

  View details for Web of Science ID 000388661700002

  View details for PubMedID 26347016

  View details for PubMedCentralID PMC4559218

• Fabrication of healthy and disease-mimicking retinal phantoms with tapered foveal pits for optical coherence tomography. Journal of biomedical optics Lee, G. C., Smith, G. T., Agrawal, M., Leng, T., Ellerbee, A. K. 2015; 20 (8): 85004-?

  View details for DOI 10.1117/1.JBO.20.8.085004

  View details for PubMedID 26287985

• Fabrication of healthy and disease-mimicking retinal phantoms with tapered foveal pits for optical coherence tomography. Journal of biomedical optics Lee, G. C., Smith, G. T., Agrawal, M., Leng, T., Ellerbee, A. K. 2015; 20 (8): 85004-?

  View details for DOI 10.1117/1.JBO.20.8.085004

  View details for PubMedID 26287985

• Visual Prognosis of Eyes Recovering From Macular Hole Surgery Through Automated Quantitative Analysis of Spectral-Domain Optical Coherence Tomography (SD-OCT) Scans. Investigative ophthalmology & visual science de Sisternes, L., Hu, J., Rubin, D. L., Leng, T. 2015; 56 (8): 4631-4643

  Abstract

  To determine the value of topographic spectral-domain optical coherence tomography (SD-OCT) imaging features assessed after macular hole repair surgery in predicting visual acuity (VA) outcomes.An automated algorithm was developed to topographically outline and quantify area, extent, and location of defects in the ellipsoid zone (EZ) band and inner retina layers in SD-OCT scans. We analyzed the correlation of these values with VA in longitudinal observations from 35 patients who underwent successful macular hole surgery, in their first observation after surgery (within 2 months), and in a single observation within 6 to 12 months after surgery. Image features assessed at the first visit after surgery were also investigated as possible predictors of future VA improvement.Significant correlation with longitudinal VA was found for the extent, circularity, and ratio of defects in EZ band at the fovea and parafoveal regions. The ratio of defects in EZ band at the fovea, temporal-inner, and inferior-inner macula regions showed significant strong correlation with VA within 6 to 12 months post surgery. Patients with worse vision outcome at such time also had a significantly higher rate of inner retinal defects in the superior-outer region in their first postsurgery observation.A lowering extent of EZ band defects in the foveal and parafoveal regions is a good indicator of postsurgery VA recovery. Attention should also be given to postsurgical alterations in the inner retina, as patients with more extensive atrophic changes appear to have slower or worse VA recovery despite closure of the macular hole.

  View details for DOI 10.1167/iovs.14-16344

  View details for PubMedID 26200503

  View details for PubMedCentralID PMC4515949

• Application of Improved Homogeneity Similarity-Based Denoising in Optical Coherence Tomography Retinal Images JOURNAL OF DIGITAL IMAGING Chen, Q., de Sisternes, L., Leng, T., Rubin, D. L. 2015; 28 (3): 346-361

  Abstract

  Image denoising is a fundamental preprocessing step of image processing in many applications developed for optical coherence tomography (OCT) retinal imaging-a high-resolution modality for evaluating disease in the eye. To make a homogeneity similarity-based image denoising method more suitable for OCT image removal, we improve it by considering the noise and retinal characteristics of OCT images in two respects: (1) median filtering preprocessing is used to make the noise distribution of OCT images more suitable for patch-based methods; (2) a rectangle neighborhood and region restriction are adopted to accommodate the horizontal stretching of retinal structures when observed in OCT images. As a performance measurement of the proposed technique, we tested the method on real and synthetic noisy retinal OCT images and compared the results with other well-known spatial denoising methods, including bilateral filtering, five partial differential equation (PDE)-based methods, and three patch-based methods. Our results indicate that our proposed method seems suitable for retinal OCT imaging denoising, and that, in general, patch-based methods can achieve better visual denoising results than point-based methods in this type of imaging, because the image patch can better represent the structured information in the images than a single pixel. However, the time complexity of the patch-based methods is substantially higher than that of the others.

  View details for DOI 10.1007/s10278-014-9742-8

  View details for Web of Science ID 000354950200014

  View details for PubMedID 25404105

• Experience With Aflibercept for the Treatment of Neovascular Age-Related Macular Degeneration. Ophthalmic surgery, lasers & imaging retina He, L., Silva, R. A., Ayoub, N., Moshfeghi, D. M., Leng, T. 2015; 46 (5): 542-549

  Abstract

  Describe visual and anatomic outcomes of eyes with exudative age- related macular degeneration (AMD) after treatment with aflibercept.Eyes treated with intravitreal injections of aflibercept for exudative AMD were retrospectively reviewed to compare visual acuity and central subfield thickness (CST) on optical coherence tomography.A total of 142 eyes receiving aflibercept were previously treated with bevacizumab or ranibizumab intravitreal injections. Baseline vision was 20/73 ± 5.18 lines when switched to aflibercept. It improved by 0.2 ± 1.91 lines (P =.14) after three injections but decreased by 0.45 ± 2.9 lines (P = .06) after 1 year of follow-up. The reduction in CST was 9.9 ± 46.5 µm (P = .06) after three injections and grew to 19.3 ± 50.6 µm (P = .002), a statistically significant amount, after 1 year.Switching to aflibercept resulted in no clinically significant differences in visual acuity after 1 year. There was a significant reduction in CST, but this may not be clinically significant.

  View details for DOI 10.3928/23258160-20150521-05

  View details for PubMedID 26057757

• SUNDROP: six years of screening for retinopathy of prematurity with telemedicine. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie Wang, S. K., Callaway, N. F., Wallenstein, M. B., Henderson, M. T., Leng, T., Moshfeghi, D. M. 2015; 50 (2): 101-106

  Abstract

  To report the 6-year results of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) initiative in the context of telemedicine screening initiatives for retinopathy of prematurity (ROP).A retrospective analysis.Premature newborns requiring ROP screening at 6 neonatal intensive care units from December 1, 2005, to November 30, 2011.Infants were evaluated via remote retinal photography by an ROP specialist. A total of 608 preterm infants meeting ROP examination criteria were screened with the RetCam II/III (Clarity Medical Systems, Pleasanton, Calif.). Primary outcomes were treatment-warranted ROP (TW-ROP) and adverse anatomical events.During the 6 years, 1216 total eyes were screened during 2169 examinations, generating 26 970 retinal images, an average of 3.56 examinations and 44.28 images per patient. Twenty-two (3.6%) of the infants screened met criteria for TW-ROP. Compared with bedside binocular ophthalmoscopy, remote interpretation of RetCam II/III images had a sensitivity of 100%, specificity of 99.8%, positive predicative value of 95.5%, and negative predicative value of 100% for the detection of TW-ROP. No adverse anatomical outcomes were observed for any enrolled patient.The 6-year results for the SUNDROP telemedicine initiative were highly favourable with respect to diagnostic accuracy. Telemedicine appears to be a safe, reliable, and cost-effective complement to the efforts of ROP specialists, capable of increasing patient access to screening and focusing the resources of the current ophthalmic community on infants with potentially vision-threatening disease.

  View details for DOI 10.1016/j.jcjo.2014.11.005

  View details for PubMedID 25863848

• Acute Retinal Necrosis Secondary to Herpes Simplex Virus Type 2 in Neonates OPHTHALMIC SURGERY LASERS & IMAGING RETINA Venincasa, V. D., Emanuelli, A., Leng, T., Perlini, E., Villegas, V., Diaz-Barbosa, M., Gutierrez, M., Miller, D., Berrocal, A. M. 2015; 46 (4): 499-501

  Abstract

  Acute retinal necrosis (ARN) should be in the differential diagnosis of a neonate who presents with vitritis. This report includes three cases of neonatal ARN at the Bascom Palmer Eye Institute from 2004 to 2009. Medical treatment with acyclovir helped reduce sequelae of herpes simplex virus (HSV) 2 infection. Patients with ARN are at risk for retinal detachment and blindness. Although mothers are screened during pregnancy, they are at risk of reactivation or primary contraction of HSV. A neonate presenting with vitritis should raise suspicion of ARN. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:499-501.].

  View details for DOI 10.3928/23258160-20150422-18

  View details for Web of Science ID 000359292300018

  View details for PubMedID 25932732

• Risk factors for respiratory depression in patients undergoing retrobulbar block for vitreoretinal surgery. Ophthalmic surgery, lasers & imaging retina Silva, R. A., Leng, J. C., He, L., Brock-Utne, J. G., Drover, D. R., Leng, T. 2015; 46 (2): 243-247

  Abstract

  To determine the risk factors for respiratory depression during retrobulbar block administration before vitreoretinal surgery.Prospective, observational case series of 113 patients undergoing monitored anesthesia care and retrobulbar block before vitreoretinal surgery at a tertiary medical center.Chin lift, jaw thrust, and bag mask ventilation were performed in eight (7.1%), nine (8%), and six (5.3%) patients, respectively. No patients required intubation. Age, sex, body mass index, history of obstructive sleep apnea, American Society of Anesthesiologists physical status level, and baseline oxygen saturation were not predictive of airway intervention. Of the four anesthetic agents utilized (midazolam, fentanyl, alfentanil, and propofol), only propofol and fentanyl were associated with an increased risk for clinically significant apnea. Use of three medications for sedation was associated with a 5.4-fold increase in the relative risk of requiring a respiratory rescue intervention.During preoperative sedation for retrobulbar block administration, the use of propofol, fentanyl, or a combination of three anesthetics is associated with a statistically significant increase in the risk for respiratory depression requiring resuscitation. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:243-247.].

  View details for DOI 10.3928/23258160-20150213-22

  View details for PubMedID 25707051

• Stem cell treatments: What's happening in 2015 Retinal Physician Leng, T. 2015: 48-50
• West African Crystalline Maculopathy in Sickle Cell Retinopathy. Case reports in ophthalmological medicine Kung, J. S., Leng, T. 2015; 2015: 910713-?

  Abstract

  Purpose. To describe the first reported case of West African crystalline maculopathy (WACM) from a member of the Benin tribe and explore the association with sickle cell retinopathy. Methods. Full ophthalmic examination and high-resolution ocular coherence tomographic imaging. Patients. 61-year-old patient from an academic retina practice. Results. The patient demonstrated bilateral yellow-green birefringent crystals localized to the inner retina on optical coherence tomography, as well as sickle cell-related neovascularization in the right eye. She reported no consumption of kola nuts. Conclusions. Associated retinal vascular disease may be important in the pathogenesis of crystalline maculopathy.

  View details for DOI 10.1155/2015/910713

  View details for PubMedID 26788391

  View details for PubMedCentralID PMC4695655

• Idiopathic pigmented vitreous cyst. Acta ophthalmologica Ludwig, C. A., Leng, T. n. 2015

  View details for PubMedID 26095667

• A FALSE COLOR FUSION STRATEGY FOR DRUSEN AND GEOGRAPHIC ATROPHY VISUALIZATION IN OPTICAL COHERENCE TOMOGRAPHY IMAGES RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Chen, Q., Leng, T., Niu, S., Shi, J., de Sisternes, L., Rubin, D. L. 2014; 34 (12): 2346-2358

  Abstract

  To display drusen and geographic atrophy (GA) in a single projection image from three-dimensional spectral domain optical coherence tomography images based on a novel false color fusion strategy.We present a false color fusion strategy to combine drusen and GA projection images. The drusen projection image is generated with a restricted summed-voxel projection (axial sum of the reflectivity values in a spectral domain optical coherence tomography cube, limited to the region where drusen is present). The GA projection image is generated by incorporating two GA characteristics: bright choroid and thin retina pigment epithelium. The false color fusion method was evaluated in 82 three-dimensional optical coherence tomography data sets obtained from 7 patients, for which 2 readers independently identified drusen and GA as the gold standard. The mean drusen and GA overlap ratio was used as the metric to determine accuracy of visualization of the proposed method when compared with the conventional summed-voxel projection, (axial sum of the reflectivity values in the complete spectral domain optical coherence tomography cube) technique and color fundus photographs.Comparative results demonstrate that the false color image is more effective in displaying drusen and GA than summed-voxel projection and CFP. The mean drusen/GA overlap ratios based on the conventional summed-voxel projection method, color fundus photographs, and the false color fusion method were 6.4%/100%, 64.1%/66.7%, and 85.6%/100%, respectively.The false color fusion method was more effective for simultaneous visualization of drusen and GA than the conventional summed-voxel projection method and color fundus photographs, and it seems promising as an alternative method for visualizing drusen and GA in the retinal fundus, which commonly occur together and can be confusing to differentiate without methods such as this proposed one.

  View details for Web of Science ID 000345911300010

  View details for PubMedID 25062439

• Quantitative SD-OCT imaging biomarkers as indicators of age-related macular degeneration progression. Investigative ophthalmology & visual science de Sisternes, L., Simon, N., Tibshirani, R., Leng, T., Rubin, D. L. 2014; 55 (11): 7093-7103

  Abstract

  Purpose: We developed a statistical model based on quantitative characteristics of drusen to estimate the likelihood of conversion from early and intermediate age-related macular degeneration (AMD) to its advanced exudative form (AMD progression) in the short term (less than 5 years), a crucial task to enable early intervention and improve outcomes. Methods: Image features of drusen quantifying their number, morphology, and reflectivity properties, as well as the longitudinal evolution in these characteristics, were automatically extracted from 2146 spectral domain optical coherence tomography (SD-OCT) scans of 330 AMD eyes in 244 patients collected over a period of 5 years, with 36 eyes showing progression during clinical follow-up. We developed and evaluated a statistical model to predict the likelihood of progression at pre-determined times using clinical and image features as predictors. Results: Area, volume, height, and reflectivity of drusen were informative features distinguishing between progressing and non-progressing cases. Discerning progression at follow-up (mean 6.16 months) resulted in a mean area under the receiver operating characteristic curve (AUC) of 0.74 ((0.58, 0.85) 95% confidence interval (CI)). The maximum predictive performance was observed at 11 months after a patient's first early AMD diagnosis, with mean AUC 0.92 ((0.83, 0.98) 95% CI). Those eyes predicted to progress showed a much higher progression rate than those predicted not to progress at any given time from the initial visit. Conclusions: Our results demonstrate the potential ability of our model to identify those AMD patients at risk of progressing to exudative AMD from an early or intermediate stage.

  View details for DOI 10.1167/iovs.14-14918

  View details for PubMedID 25301882

• Optic nerve pit-associated choroidal cleft. JAMA ophthalmology Silva, R. A., Chang, R. T., Moshfeghi, D. M., Leng, T. 2014; 132 (9): 1142-?

  View details for DOI 10.1001/jamaophthalmol.2014.174

  View details for PubMedID 25058335

• Multimodal imaging and multifocal electroretinography demonstrate autosomal recessive Stargardt disease may present like occult macular dystrophy. Retina (Philadelphia, Pa.) Sisk, R. A., Leng, T. 2014; 34 (8): 1567-75

  Abstract

  To describe multimodal imaging and electrophysiologic characteristics of an unusual subset of patients with genetically confirmed autosomal recessive Stargardt disease (STGD1) who exhibited a central form of cone dysfunction resembling occult macular dystrophy that preceded the development of lipofuscin flecks, atrophy of retinal pigment epithelium (RPE), or full-field electroretinography abnormalities.Retrospective, observational descriptive case series.Five patients with compound heterozygous ABCA4 mutations presented with bilateral visual acuity reduction, normal-appearing fundi, and blocked choroidal fluorescence on fluorescein angiography. One sibling each of two probands with identical genotypes was also included for analysis. Full-field electroretinography testing was normal in all patients, but multifocal electroretinography demonstrated centripetally depressed amplitudes exceeding areas of fundus autofluorescence, infrared imaging, and spectral domain optical coherence tomography abnormalities. Spectral domain optical coherence tomography initially revealed disruption of the inner segment ellipsoid band accompanying an ovoid hypofluorescent foveolar lesion. Progression to later stages was accompanied by the loss of the foveal photoreceptor outer segments, creating foveal cavitation with preservation of the RPE. Fundus autofluorescence and infrared imaging demonstrated corresponding bull's eye lesions. Over time, the foveal potential space on spectral domain optical coherence tomography collapsed, and three patients developed RPE atrophy and visible lipofuscin flecks. The flecks were detectable by fundus autofluorescence and infrared imaging earlier than by biomicroscopy. From these findings, a staging system for this subset of Stargardt disease presenting with central cone dysfunction was developed and presented herein.Autosomal recessive Stargardt disease may present as a central cone dysfunction syndrome before the development of lipofuscin flecks, atrophy of RPE, or full-field electroretinography abnormalities. If emerging therapies for Stargardt disease succeed, early recognition and treatment of patients with preserved foveal photoreceptor and RPE cell bodies may yield a more favorable visual prognosis.

  View details for DOI 10.1097/IAE.0000000000000136

  View details for PubMedID 24743636

• An improved optical coherence tomography-derived fundus projection image for drusen visualization. Retina (Philadelphia, Pa.) Chen, Q., Leng, T., Zheng, L. L., Kutzscher, L., de Sisternes, L., Rubin, D. L. 2014; 34 (5): 996-1005

  Abstract

  To develop and evaluate an improved method of generating en face fundus images from three-dimensional optical coherence tomography images which enhances the visualization of drusen.We describe a novel approach, the restricted summed-voxel projection (RSVP), to generate en face projection images of the retinal surface combined with an image processing method to enhance drusen visualization. The RSVP approach is an automated method that restricts the projection to the retinal pigment epithelium layer neighborhood. Additionally, drusen visualization is improved through an image processing technique that fills drusen with bright pixels. The choroid layer is also excluded when creating the RSVP to eliminate bright pixels beneath drusen that could be confused with drusen when geographic atrophy is present. The RSVP method was evaluated in 46 patients and 3-dimensional optical coherence tomography data sets were obtained from 8 patients, for which 2 readers independently identified drusen as the gold standard. The mean drusen overlap ratio was used as the metric to determine the accuracy of visualization of the RSVP method when compared with the conventional summed-voxel projection technique.Comparative results demonstrate that the RSVP method was more effective than the conventional summed-voxel projection in displaying drusen and retinal vessels, and was more useful in detecting drusen. The mean drusen overlap ratios based on the conventional summed-voxel projection method and the RSVP method were 2.1% and 89.3%, respectively.The RSVP method was more effective for drusen visualization than the conventional summed-voxel projection method, and it may be useful for macular assessment in patients with nonexudative age-related macular degeneration.

  View details for DOI 10.1097/IAE.0000000000000018

  View details for PubMedID 24177190

• Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): five years of screening with telemedicine. Ophthalmic surgery, lasers & imaging retina Fijalkowski, N., Zheng, L. L., Henderson, M. T., Wang, S. K., Wallenstein, M. B., Leng, T., Moshfeghi, D. M. 2014; 45 (2): 106-113

  Abstract

  To report the 5-year results of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative.Infants requiring retinopathy of prematurity (ROP) screening at six neonatal intensive care units from December 1, 2005, to November 30, 2010, were evaluated with remote retinal photography by an ROP specialist. Every infant received outpatient binocular indirect ophthalmoscope examinations until termination criteria were achieved or until treatment. Outcomes were treatment-warranted ROP (TW-ROP, ETROP type 1) and adverse anatomical events.Five hundred eleven infants (1,022 eyes) were screened. Fifteen infants had TW-ROP and underwent laser photocoagulation. The TW-ROP cohort had significantly lower birth weight and gestational age (both P < .001). No patient progressed to adverse anatomical outcomes and no case of TW-ROP was missed. Tele-medicine had 100% sensitivity, 99.8% specificity, 93.8% positive predictive value, and 100% negative predictive value for detection of TW-ROP.Telemedicine demonstrates high diagnostic accuracy for detection of TW-ROP and can complement ROP screening. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:106-113.].

  View details for DOI 10.3928/23258160-20140122-01

  View details for PubMedID 24444469

• Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): Five Years of Screening With Telemedicine. Ophthalmic surgery, lasers & imaging retina Fijalkowski, N., Zheng, L. L., Henderson, M. T., Wang, S. K., Wallenstein, M. B., Leng, T., Moshfeghi, D. M. 2014; 45 (2): 106-113

  View details for DOI 10.3928/23258160-20140122-01

  View details for PubMedID 24444469

• Retinal breaks due to intravitreal ocriplasmin. Clinical ophthalmology (Auckland, N.Z.) Silva, R. A., Moshfeghi, D. M., Leng, T. 2014; 8: 1591-1594

  Abstract

  Ocriplasmin represents a new treatment option for numerous vitreoretinopathies involving an abnormal vitreomacular interface. While the drug may circumvent the traditional risks of surgical treatment, pharmacologic vitreolysis is not devoid of risk itself. This report presents two cases, one of vitreomacular traction syndrome and the other of a full-thickness macular hole, both of which were treated with an intravitreal injection of ocriplasmin. Notably, in both cases, vitreomacular traction of the macula appears to have been alleviated; however, failure to completely relieve vitreoretinal traction from the peripheral retina generated retinal breaks with one patient eventually developing a macula-involving retinal detachment. Thus, even in instances of 'successful' pharmacologic treatment of vitreomacular traction, continued follow-up evaluation is essential.

  View details for DOI 10.2147/OPTH.S68037

  View details for PubMedID 25210426

• Automated drusen segmentation and quantification in SD-OCT images. Medical image analysis Chen, Q., Leng, T., Zheng, L., Kutzscher, L., Ma, J., de Sisternes, L., Rubin, D. L. 2013; 17 (8): 1058-1072

  Abstract

  Spectral domain optical coherence tomography (SD-OCT) is a useful tool for the visualization of drusen, a retinal abnormality seen in patients with age-related macular degeneration (AMD); however, objective assessment of drusen is thwarted by the lack of a method to robustly quantify these lesions on serial OCT images. Here, we describe an automatic drusen segmentation method for SD-OCT retinal images, which leverages a priori knowledge of normal retinal morphology and anatomical features. The highly reflective and locally connected pixels located below the retinal nerve fiber layer (RNFL) are used to generate a segmentation of the retinal pigment epithelium (RPE) layer. The observed and expected contours of the RPE layer are obtained by interpolating and fitting the shape of the segmented RPE layer, respectively. The areas located between the interpolated and fitted RPE shapes (which have nonzero area when drusen occurs) are marked as drusen. To enhance drusen quantification, we also developed a novel method of retinal projection to generate an en face retinal image based on the RPE extraction, which improves the quality of drusen visualization over the current approach to producing retinal projections from SD-OCT images based on a summed-voxel projection (SVP), and it provides a means of obtaining quantitative features of drusen in the en face projection. Visualization of the segmented drusen is refined through several post-processing steps, drusen detection to eliminate false positive detections on consecutive slices, drusen refinement on a projection view of drusen, and drusen smoothing. Experimental evaluation results demonstrate that our method is effective for drusen segmentation. In a preliminary analysis of the potential clinical utility of our methods, quantitative drusen measurements, such as area and volume, can be correlated with the drusen progression in non-exudative AMD, suggesting that our approach may produce useful quantitative imaging biomarkers to follow this disease and predict patient outcome.

  View details for DOI 10.1016/j.media.2013.06.003

  View details for PubMedID 23880375

• Semi-automatic geographic atrophy segmentation for SD-OCT images BIOMEDICAL OPTICS EXPRESS Chen, Q., de Sisternes, L., Leng, T., Zheng, L., Kutzscher, L., Rubin, D. L. 2013; 4 (12): 2729-2750

  Abstract

  Geographic atrophy (GA) is a condition that is associated with retinal thinning and loss of the retinal pigment epithelium (RPE) layer. It appears in advanced stages of non-exudative age-related macular degeneration (AMD) and can lead to vision loss. We present a semi-automated GA segmentation algorithm for spectral-domain optical coherence tomography (SD-OCT) images. The method first identifies and segments a surface between the RPE and the choroid to generate retinal projection images in which the projection region is restricted to a sub-volume of the retina where the presence of GA can be identified. Subsequently, a geometric active contour model is employed to automatically detect and segment the extent of GA in the projection images. Two image data sets, consisting on 55 SD-OCT scans from twelve eyes in eight patients with GA and 56 SD-OCT scans from 56 eyes in 56 patients with GA, respectively, were utilized to qualitatively and quantitatively evaluate the proposed GA segmentation method. Experimental results suggest that the proposed algorithm can achieve high segmentation accuracy. The mean GA overlap ratios between our proposed method and outlines drawn in the SD-OCT scans, our method and outlines drawn in the fundus auto-fluorescence (FAF) images, and the commercial software (Carl Zeiss Meditec proprietary software, Cirrus version 6.0) and outlines drawn in FAF images were 72.60%, 65.88% and 59.83%, respectively.

  View details for DOI 10.1364/BOE.4.002729

  View details for Web of Science ID 000328078300002

  View details for PubMedID 24409376

  View details for PubMedCentralID PMC3862151

• Traumatic airbag maculopathy. JAMA ophthalmology Kung, J., Leung, L. B., Leng, T., Liao, Y. J. 2013; 131 (5): 685-687

  View details for DOI 10.1001/jamaophthalmol.2013.883

  View details for PubMedID 23699847

• Quantitative evaluation of drusen on photographs. Ophthalmology Rubin, D. L., de Sisternes, L., Kutzscher, L., Chen, Q., Leng, T., Zheng, L. L. 2013; 120 (3): 644-644 e2

  View details for DOI 10.1016/j.ophtha.2012.09.052

  View details for PubMedID 23714606

• Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): Four-years of Screening with Telemedicine CURRENT EYE RESEARCH Fijalkowski, N., Zheng, L. L., Henderson, M. T., Wallenstein, M. B., Leng, T., Moshfeghi, D. M. 2013; 38 (2): 283-291

  Abstract

  To report the four-year experience of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative, which was developed to reduce the risk of blindness from retinopathy of prematurity (ROP).A retrospective analysis of the SUNDROP archival data between 12/1/2005 and 11/30/2009. A total of 410 consecutively enrolled infants meeting ROP screening criteria had nurse-obtained fundoscopic images evaluated remotely by an ROP specialist. Every infant then received at least one dilated bedside binocular indirect ophthalmoscope (BIO) examination within one week of discharge. All infants were then followed with both telemedicine images and bedside evaluation in clinic according to recommended screening timelines. Primary outcomes were treatment-warranted ROP (TW-ROP), defined as Early Treatment of ROP Type 1, and adverse anatomical outcomes.The SUNDROP telemedicine screening initiative has not missed any TW-ROP in its four-year evaluation period. A total of 410 infants (820 eyes) were imaged, resulting in 1486 examinations and 18,097 unique images. An average of 12.2 images were obtained per patient. Fourteen infants met TW-ROP criteria on telemedicine examination. After bedside evaluation, 13 infants required laser photocoagulation and one was followed until he spontaneously regressed. Infants with TW-ROP had a significantly lower gestational age (24.9 weeks), birth weight (658.7 grams), and were more likely to be male than the no TW-ROP cohort (all p values <0.00001). Telemedicine had a calculated sensitivity of 100%, specificity of 99.8%, positive predicative value of 92.9% and negative predictive value of 100% for the detection of TW-ROP. No patient progressed to retinal detachment or any adverse anatomical outcome.The SUNDROP initiative demonstrated a high degree of diagnostic reliability and was able to capture all infants with TW-ROP. Telemedicine offers a cost-effective, reliable and accurate screening methodology for identifying infants with TW-ROP without sacrificing quality of care.

  View details for DOI 10.3109/02713683.2012.754902

  View details for Web of Science ID 000314900400008

  View details for PubMedID 23330739

• Abundance of myelinated nerve fibers. JAMA ophthalmology Leng, T., Nyong'o, O. L. 2013; 131 (2): 245-?

  View details for DOI 10.1001/jamaophthalmol.2013.583

  View details for PubMedID 23411895

• Antibiotic controversies in vitreoretinal practice Retinal Physician Karth, P. A., Leng, T. 2013: 22-25
• Management of suspected endogenous endophthalmitis Retina Today Leng, T. 2013; 8 (6): 32-33
• Carbon nanotube bucky paper as an artificial support membrane for retinal cell transplantation. Ophthalmic surgery, lasers & imaging retina Leng, T., Fishman, H. A. 2013; 44 (1): 73-76

  Abstract

  Transplantation of epithelial cells on a substrate to rescue diseased retinal cells is an experimental therapy for age-related macular degeneration. Carbon nanotube bucky paper was tested for cell transplantation into the retina.Bucky paper was prepared and human RPE cells cultured on its surface demonstrating its utility as a cell transplantation substrate. Bucky paper was implanted underneath 9 rabbit retinas using a standard 3-port pars plana vitrectomy and subretinal bleb. A 1 mm retinotomy was created through which Bucky paper precut to fit was inserted with the subretinal forceps, into the subretinal bleb. The retina was reattached by airfluid exchange.By light microscopy, RPE cells demonstrated normal morphology and growth patterns on the bucky paper surface. Scanning electron microscopy confirmed a confluent monolayer of cells, and indicated the formation of microvilli on the apical surface. Bucky paper remained flat in the subretinal space after 2 weeks, the retina fully attached without edema or inflammation.Bucky paper possesses the necessary attributes for therapeutic cell transplantation in the eye.

  View details for DOI 10.3928/23258160-20121221-16

  View details for PubMedID 23410811

• FOVEAL CAVITATION AS AN OPTICAL COHERENCE TOMOGRAPHY FINDING IN CENTRAL CONE DYSFUNCTION RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., Marmor, M. F., Kellner, U., Thompson, D. A., Renner, A. B., Moore, W., Sowden, J. C. 2012; 32 (7): 1411-1419

  Abstract

  To describe a distinctive foveal cavitation as seen by spectral-domain optical coherence tomography in certain cone dysfunction syndromes.Observational case series. Patients were evaluated by dilated fundus examination, fundus photography, fundus autofluorescence, full-field electroretinogram, multifocal electroretinogram, spectral-domain optical coherence tomography, color vision testing, fluorescein angiography, Goldmann visual field testing, and molecular genetic analysis.We present eight patients with foveal cavitation in association with presumed cone dysfunction. This was characterized on spectral-domain optical coherence tomography by a gap in the subfoveal outer segment layer without more diffuse retinal thinning. There were 5 patients of age 10 years to 27 years and 3 patients of age 49 years to 52 years, with a 1.5- to 38-year history of bilateral visual loss. A small foveal oval-shaped area of reduced foveal fundus autofluorescence, surrounded by increased fundus autofluorescence, was seen in the younger patients, and a broad circle of increased fundus autofluorescence in the older patients. The multifocal electroretinogram always showed central amplitude reduction, but there were varying degrees of cone dysfunction on full-field electroretinogram. There were mild abnormalities on desaturated color vision testing. The family history was noncontributory in all cases. None of the cases were congenital. ABCA4 gene mutations were identified in three of five patients tested; CNGB3 testing was negative in these patients.Cone dysfunction syndromes typically show retinal thinning on optical coherence tomography imaging, although several case reports have noted focal outer retinal loss. Our case series shows that a distinctive optical coherence tomography finding, foveal cavitation, may be a clue to cone dysfunction syndromes, but is not specific to any one hereditary disorder or age group.

  View details for DOI 10.1097/IAE.0b013e318236e4ea

  View details for PubMedID 22466470

• Cannula-Based 25-Gauge Vitreous Tap And Injection: A New Surgical Technique RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Chan, A., Leng, T., Moshfeghi, D. M. 2012; 32 (5): 1021-1022

  View details for DOI 10.1097/IAE.0b013e318248e6ba

  View details for PubMedID 22311272

• Effect of Lidocaine Gel Anesthesia on Endophthalmitis Rates Following Intravitreal Injection OPHTHALMIC SURGERY LASERS & IMAGING Lad, E. M., Maltenfort, M. G., Leng, T. 2012; 43 (2): 115-120

  Abstract

  To determine whether the use of lidocaine gel before application of povidone-iodine affects endophthalmitis rates following intravitreal injections.Retrospective consecutive case series of all intravitreal injections and post-intravitreal injection endophthalmitis cases at one institution from 2000 to 2009. A review of medical records of post-intravitreal injection endophthalmitis cases was performed to determine whether lidocaine gel was applied prior to povidone-iodine antisepsis and to analyze the clinical course and outcomes.A total of 8,802 intravitreal injections were administered during the study period. When no lidocaine gel was used prior to povidone-iodine antisepsis, four cases of endophthalmitis following 4,120 intravitreal injections (0.097%) were recorded. When 2% lidocaine gel was applied before povidone-iodine, four cases of endophthalmitis following 4,682 intravitreal injections (0.085%) were observed (P = 1.00, odds ratio = 1.12).The use of lidocaine gel prior to povidone-iodine antisepsis did not significantly alter post-intravitreal injection endophthalmitis rates.

  View details for DOI 10.3928/15428877-20120119-01

  View details for Web of Science ID 000305342900004

  View details for PubMedID 22283227

• REDUCING ORAL FLORA CONTAMINATION OF INTRAVITREAL INJECTIONS WITH FACE MASK OR SILENCE RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Doshi, R. R., Leng, T., Fung, A. E. 2012; 32 (3): 473-476

  Abstract

  To provide experimental evidence to support or refute the proposition that the use of surgical face masks and/or avoidance of talking can decrease the dispersion of respiratory flora during an intravitreal injection.Ten surgeons recited a 30-second standardized script with blood agar plates positioned 30 cm below their mouths. The plates were divided into 4 groups, with 10 plates per group. In Group 1, participants did not wear a face mask. In Group 2, participants wore a standard surgical mask. In Group 3, no mask was worn, but plates were pretreated with 5% povidone-iodine. In Group 4, no mask was worn, and participants remained silent for 30 seconds. The plates were then incubated at 37°C for 24 hours, and the number of colony-forming units (CFUs) was determined.Mean bacterial growth were as follows: Group 1, 8.6 CFUs per subject; Group 2, 1.1 CFUs per subject; Group 3, 0.1 CFUs per subject; and Group 4, 2.4 CFUs per subject. Differences between the groups were statistically significant (P < 0.05), with the exception of Group 2 versus Group 4 (P = 0.115).The use of a face mask and avoidance of talking each significantly decreased the dispersion of bacteria. Even without these interventions, plates pretreated with povidone-iodine demonstrated the least bacterial growth.

  View details for DOI 10.1097/IAE.0B013E31822C2958

  View details for Web of Science ID 000300907200007

  View details for PubMedID 22374155

• The influence of medical school and residency training program upon choice of an academic career and academic productivity among otolaryngology faculty in the United States of America: Our experience of 1433 academic otolaryngologists CLINICAL OTOLARYNGOLOGY Leng, T., Jaben, K. A., Zheng, L., Yang, J., Paulus, Y. M., Moshfeghi, A. A., Maltenfort, M. G., Campbell, P. G., Ratliff, J. K., Moshfeghi, D. M. 2012; 37 (1): 58-62

  View details for DOI 10.1111/j.1749-4486.2011.02402.x

  View details for Web of Science ID 000301779300008

  View details for PubMedID 22433138

• Two cases of X-linked retinoschisis with different spectral domain optical coherence tomography findings. Clinical ophthalmology (Auckland, N.Z.) Leng, T. 2012; 6: 1563-1565

  Abstract

  Spectral domain optical coherence tomography was used to image the maculae of two brothers who had the diagnosis of X-linked retinoschisis maculopathy. One patient demonstrated a large foveal cyst in one eye and a lamellar macular hole in the fellow eye. The second patient demonstrated small retinal cysts in multiple layers of the retina. Spectral domain optical coherence tomography allowed high-resolution imaging and characterization of the features in X-linked retinoschisis in these patients, and it highlighted the variability of the same genetic disease, even in one family.

  View details for DOI 10.2147/OPTH.S36756

  View details for PubMedID 23055679

  View details for PubMedCentralID PMC3460697

• Intravitreal dexamethasone in the management of delayed-onset bleb-associated endophthalmitis. International journal of inflammation Jacobs, D. J., Pathengay, A., Flynn, H. W., Leng, T., Miller, D., Shi, W. 2012; 2012: 503912-?

  Abstract

  Purpose. To report the visual acuity (VA) outcomes and culture results of delayed-onset bleb-associated endophthalmitis (BAE) with and without intravitreal dexamethasone (IVD). Methods. Retrospective nonrandomized comparative case series of BAE at Bascom Palmer Eye Institute between January 1, 1996 and December 31, 2009. Clinical data were compared using the 2-sided Student's t-test for patients who received IVD and patients who did not receive IVD. Results. 70/83 (84%) received IVD, and 13/83 (16%) did not receive IVD. Mean baseline VA was 20/90 in the IVD group and 20/70 in the group that did not receive IVD (P = 0.57). Mean presenting VA was 0.9/200 in the IVD group and 1.7/200 in the group that did not receive IVD (P = 0.23). Repeat cultures were positive in 2/70 (3%) IVD cases and 1/13 (8%) cases that did not receive IVD (P = 0.57). Mean VA at 1 month was 5/200 in the IVD group and 1.8/200 in the group that did not receive IVD, logMARΔ of 0.85 and 1.56, respectively (P = 0.02). Mean VA at 3 months was 7/200 in the IVD group and 3/200 in the group that did not receive IVD, logMARΔ of 0.74 and 1.33, respectively (P = 0.14). Conclusion. In the current study of BAE, IVD was associated with improved short-term VA outcomes without an increased rate of persistent infection.

  View details for DOI 10.1155/2012/503912

  View details for PubMedID 22288020

  View details for PubMedCentralID PMC3263617

• Medical School and Residency Influence on Choice of an Academic Career and Academic Productivity Among US Neurology Faculty ARCHIVES OF NEUROLOGY Campbell, P. G., Lee, Y. H., Bell, R. D., Maltenfort, M. G., Moshfeghi, D. M., Leng, T., Moshfeghi, A. A., Ratliff, J. K. 2011; 68 (8): 999-1004

  Abstract

  To evaluate the effectiveness of medical schools and neurology training programs in the United States by determining their contribution to academic neurology in terms of how many graduates choose academic careers and their respective influence on current medical knowledge through bibliometric analysis.Biographical information from current faculty members of neurology training programs in the United States was obtained through an Internet-based search of departmental Web sites. Collected variables included medical school attended, residency program completed, and current academic rank. For each faculty member, ISI Web of Science and Scopus h -indices were also collected.Data from academic neurologists from 120 training programs with 3249 faculty members were collected. All data regarding training program and medical school education were compiled and analyzed by the institution from which each individual graduated. The 20 medical schools and neurology residency training programs producing the greatest number of graduates remaining in academic practice and the mean h -indices are reported. More medical school graduates of the Columbia University College of Physicians and Surgeons chose to enter academic neurology practice than the graduates of any other institution. Analyzed by residency training program attended, New York Presbyterian Hospital (Columbia University), Mayo Clinic (Rochester, Minnesota), and Mount Sinai Medical Center (New York, New York) produced the most graduates remaining in academics.This retrospective, longitudinal cohort study examines through quantitative measures the academic productivity and rank of academic neurologists. The results demonstrate that several training programs excel in producing a significantly higher proportion of academically active neurologists.

  View details for DOI 10.1001/archneurol.2011.67

  View details for Web of Science ID 000293647500005

  View details for PubMedID 21482917

• Medical school and residency influence on choice of an academic career and academic productivity among neurosurgery faculty in the United States Clinical article JOURNAL OF NEUROSURGERY Campbell, P. G., Awe, O. O., Maltenfort, M. G., Moshfeghi, D. M., Leng, T., Moshfeghi, A. A., Ratliff, J. K. 2011; 115 (2): 380-386

  Abstract

  Factors determining choice of an academic career in neurological surgery are unclear. This study seeks to evaluate the graduates of medical schools and US residency programs to determine those programs that produce a high number of graduates remaining within academic programs and the contribution of these graduates to academic neurosurgery as determined by h-index valuation.Biographical information from current faculty members of all accredited neurosurgery training programs in the US with departmental websites was obtained. Any individual who did not have an American Board of Neurological Surgery certificate (or was not board eligible) was excluded. The variables collected included medical school attended, residency program completed, and current academic rank. For each faculty member, Web of Science and Scopus h-indices were also collected.Ninety-seven academic neurosurgery departments with 986 faculty members were analyzed. All data regarding training program and medical school education were compiled and analyzed by center from which each faculty member graduated. The 20 medical schools and neurosurgical residency training programs producing the greatest number of graduates remaining in academic practice, and the respective individuals' h-indices, are reported. Medical school graduates of the Columbia University College of Physicians and Surgeons chose to enter academics the most frequently. The neurosurgery training program at the University of Pittsburgh produced the highest number of academic neurosurgeons in this sample.The use of quantitative measures to evaluate the academic productivity of medical school and residency graduates may provide objective measurements by which the subjective influence of training experiences on choice of an academic career may be inferred. The top 3 residency training programs were responsible for 10% of all academic neurosurgeons. The influence of medical school and residency experiences on choice of an academic career may be significant.

  View details for DOI 10.3171/2011.3.JNS101176

  View details for Web of Science ID 000293145100037

  View details for PubMedID 21495810

• Povidone-Iodine Before Lidocaine Gel Anesthesia Achieves Surface Antisepsis Annual Meeting of the Retina-Society Doshi, R. R., Leng, T., Fung, A. E. SLACK INC. 2011: 346–49

  Abstract

  Viscous lidocaine interferes with ocular surface antisepsis. The current study was designed to evaluate the impact on surface antisepsis of different application sequences with lidocaine gel and povidone-iodine solution.Blood agar plates inoculated with Staphylococcus epidermidis were treated with varying sequences of 2% lidocaine gel and 5% povidone-iodine solution. The plates were then incubated at 37°C for 24 hours and bacterial growth was determined.Plates on which povidone-iodine was applied alone or prior to lidocaine gel demonstrated no bacterial growth regardless of whether the antiseptic was retained on the plate for 5 seconds or for 30 seconds. There was no statistically significant difference between bacterial growth on plates not treated with povidone-iodine and on plates treated with lidocaine gel alone or prior to povidone-iodine (P = .553 and P = .485, respectively).Povidone-iodine effectively reduces bacterial counts when applied alone or prior to lidocaine gel. Lidocaine gel was confirmed to be a barrier to antisepsis when administered prior to povidone-iodine.

  View details for DOI 10.3928/15428877-20110210-02

  View details for Web of Science ID 000305342000012

  View details for PubMedID 21366185

• SELECTIVE RETINAL THERAPY WITH MICROSECOND EXPOSURES USING A CONTINUOUS LINE SCANNING LASER RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Paulus, Y. M., Jain, A., Nomoto, H., Sramek, C., Gariano, R. F., Andersen, D., Schuele, G., Leung, L., Leng, T., Palanker, D. 2011; 31 (2): 380-388

  Abstract

  To evaluate the safety, selectivity, and healing of retinal lesions created using a continuous line scanning laser.A 532-nm Nd:YAG laser (PASCAL) with retinal beam diameters of 40 μm and 66 μm was applied to 60 eyes of 30 Dutch-belted rabbits. Retinal exposure duration varied from 15 μs to 60 μs. Lesions were acutely assessed by ophthalmoscopy and fluorescein angiography. Retinal pigment epithelial (RPE) flatmounts were evaluated with live-dead fluorescent assay. Histological analysis was performed at 7 time points from 1 hour to 2 months.The ratios of the threshold of rupture and of ophthalmoscopic visibility to fluorescein angiography visibility (measures of safety and selectivity) increased with decreasing duration and beam diameter. Fluorescein angiography and live-dead fluorescent assay yielded similar thresholds of RPE damage. Above the ophthalmoscopic visibility threshold, histology showed focal RPE damage and photoreceptor loss at 1 day, without inner retinal effects. By 1 week, photoreceptor and RPE continuity was restored. By 1 month, photoreceptors appeared normal.: Retinal therapy with a fast scanning continuous laser achieves selective targeting of the RPE and, at higher power, of the photoreceptors without permanent scarring or inner retinal damage. Continuous scanning laser can treat large retinal areas within standard eye fixation time.

  View details for DOI 10.1097/IAE.0b013e3181e76da6

  View details for Web of Science ID 000286586500024

  View details for PubMedID 20930656

• DELAYED-ONSET BLEB-ASSOCIATED ENDOPHTHALMITIS (1996-2008) Causative Organisms and Visual Acuity Outcomes RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., Miller, D., Flynn, H. W., Jacobs, D. J., Gedde, S. J. 2011; 31 (2): 344-352

  Abstract

  The purpose of this study was to report the clinical features, organisms, and outcomes of patients with delayed-onset bleb-associated endophthalmitis.Retrospective consecutive case series. Patients who were treated for delayed-onset bleb-associated endophthalmitis between January 1, 1996, and July 1, 2008, at a single institution were included. Information on visual acuities, clinical characteristics, causative organisms, and treatment outcomes were collected. Infections within 1 month of glaucoma filtering surgery, inadvertent filtering blebs after cataract surgery, and patients with glaucoma drainage devices were excluded.A total of 71 eyes from 68 patients were identified. An adjunctive antifibrotic agent was used in 48 eyes (68%). The mean time between surgery and endophthalmitis was 4.8 years (range, 0.1-16; standard deviation, 3.6). The average follow-up time after initial treatment was 37 months (range 1-144; standard deviation, 41). At presentation, 17 eyes (24%) had a bleb leak. Fifty-seven eyes (83%) were culture positive. The most common causative organisms were Streptococcus species in 20 eyes (30%), gram-negative organisms in 19 eyes (28%), and coagulase-negative Staphylococcus in 12 eyes (18%). All gram-positive isolates were sensitive to vancomycin. Nine eyes (13%) eventually underwent evisceration or enucleation secondary to pain and/or poor vision. The main outcome measure was best-corrected visual acuity at the last follow-up examination. Final visual acuities in the initial tap/inject group (n = 45) versus the initial vitrectomy group (n = 24) were as follows: ≥ 20/40 (29% vs. 4.2%), 20/50 to 20/400 (36% vs. 29%), and <5/200 (36% vs. 62%).Streptococcus species and gram-negative organisms were the most common causative isolates identified in this case series of delayed-onset bleb-associated endophthalmitis. Despite treatment of the infection, visual outcomes were generally poor.

  View details for DOI 10.1097/IAE.0b013e3181e09810

  View details for PubMedID 20838358

• The vitreous trap: a simple, surgeon-controlled technique for obtaining undiluted vitreous and subretinal specimens during pars plana vitrectomy. Retina (Philadelphia, Pa.) Moshfeghi, A. A., Albini, T. A., Kitchens, J. W., Leng, T., Moshfeghi, D. M. 2011; 31 (2): 426-427

  View details for DOI 10.1097/IAE.0b013e318200c125

  View details for PubMedID 21233788

• Improving the therapeutic window of retinal photocoagulation by spatial and temporal modulation of the laser beam JOURNAL OF BIOMEDICAL OPTICS Sramek, C., Leung, L., Leng, T., Brown, J., Paulus, Y. M., Schuele, G., Palanker, D. 2011; 16 (2)

  Abstract

  Decreasing the pulse duration helps confine damage, shorten treatment time, and minimize pain during retinal photocoagulation. However, the safe therapeutic window (TW), the ratio of threshold powers for thermomechanical rupture of Bruch's membrane and mild coagulation, also decreases with shorter exposures. Two potential approaches toward increasing TW are investigated: (a) decreasing the central irradiance of the laser beam and (b) temporally modulating the pulse. An annular beam with adjustable central irradiance was created by coupling a 532-nm laser into a 200-μm core multimode optical fiber at a 4-7 deg angle to normal incidence. Pulse shapes were optimized using a computational model, and a waveform generator was used to drive a PASCAL photocoagulator (532 nm), producing modulated laser pulses. Acute thresholds for mild coagulation and rupture were measured in Dutch-Belted rabbit in vivo with an annular beam (154-163 μm retinal diameter) and modulated pulse (132 μm, uniform irradiance "flat-top" beam) with 2-50 ms pulse durations. Thresholds with conventional constant-power pulse and a flat-top beam were also determined. Both annular beam and modulated pulse provided a 28% increase in TW at 10-ms duration, affording the same TW as 20-ms pulses with conventional parameters.

  View details for DOI 10.1117/1.3542045

  View details for Web of Science ID 000288939200056

  View details for PubMedID 21361711

• Retinopathy of prematurity in an infant with Aicardi's syndrome EYE Leng, T., Moshfeghi, D. M. 2011; 25 (2): 257-258

  View details for DOI 10.1038/eye.2010.189

  View details for Web of Science ID 000287187300025

  View details for PubMedID 21151036

  View details for PubMedCentralID PMC3169236

• Kinetics of central macular thickness reduction in patients with macular edema after intravitreal drug therapy. Clinical ophthalmology (Auckland, N.Z.) He, L., Chan, A., Leng, T., Blumenkranz, M. S. 2011; 5: 1751-1758

  Abstract

  The purpose of this study was to characterize central macular thickness and retinal volume following intravitreal injections using time domain and spectral domain optical coherence tomography (TD-OCT and SD-OCT, respectively).Nine patients with macular edema secondary to diabetes or retinal vein occlusion treated with intravitreal triamcinolone 4.0 mg and/or bevacizumab 1.25 mg were enrolled. Central macular thickness and volume was measured by SD-OCT and TD-OCT scan at baseline, and 1, 3, 6, 24, 48 hours, and 1 week postinjection.Equations were derived to describe central macular thickness and volume reduction in the hours following intravitreal injection. Measurements of central macular thickness by SD-OCT were significantly reduced by 3 hours (P = 0.03) and retinal volume by 6 hours (P = 0.03). Central macular thickness measured 40.9 (28.6-53.2) μm thicker on the SD-OCT instrument while volume measured 3.47 (3.27-3.66) mm(3) higher.Significant central macular thickness and volume reductions occur in the first hours after injection with triamcinolone and/or bevacizumab.

  View details for DOI 10.2147/OPTH.S26631

  View details for PubMedID 22205836

  View details for PubMedCentralID PMC3245197

• Neovascularization in Purtscher's retinopathy. Clinical ophthalmology (Auckland, N.Z.) Chan, A., Fredrick, D. R., Leng, T. 2011; 5: 1585-1587

  Abstract

  We report a case of neovascularization secondary to Purtscher's retinopathy that showed minimal improvement with photocoagulation treatment. A 14-year-old boy with a history of cerebellar medulloblastoma presented with blurry vision and floaters after being struck by a motor vehicle while riding his bike. At presentation, visual acuity was 20/400 in his right eye and counting fingers in his left eye. Fundus examination showed disk edema, retinal whitening, and retinal hemorrhages in both eyes. Optical coherence tomography demonstrated thinning of the temporal retina and disruption of the inner segment-outer segment junction of the photoreceptor layer in the right eye and thickening and edema of the nasal macula, as well as a central foveal hyper-reflectivity, in the left eye. At the initial visit, there was no ischemia or neovascularization (NV). One month later, the patient developed NV of the disk and ischemia in the mid-periphery of the left eye. The patient underwent treatment with pan-retinal photocoagulation. The NV regressed, but visual outcome remained poor at his 5-month follow-up visit.

  View details for DOI 10.2147/OPTH.S26076

  View details for PubMedID 22125405

  View details for PubMedCentralID PMC3218168

• Delayed-onset bleb-associated endophthalmitis: presentation and outcome by culture result. Clinical ophthalmology (Auckland, N.Z.) Jacobs, D. J., Leng, T., Flynn, H. W., Shi, W., Miller, D., Gedde, S. J. 2011; 5: 739-744

  Abstract

  To determine how culture results are associated with clinical presentations and outcomes in delayed-onset bleb-associated endophthalmitis (BAE).Retrospective consecutive case series of BAE at Bascom Palmer Eye Institute between January 1, 1996 and December 31, 2009. All patients had prior glaucoma filtering surgery. BAE was defined as intraocular infection with vitreous involvement receiving treatment with intravitreal antibiotics. Visual acuity (VA) outcomes and other clinical data were grouped by culture result and compared using the 2-sided Student's t-test.Mean logMAR change at 3 months after treatment (3-month logMARΔ).Eighty-six eyes of 85 patients were identified. Two eyes were primarily eviscerated. Fifty-three (63%) eyes were culture-positive with the following organisms: Streptococcus, 21 (25%); coagulase-negative Staphylococcus, 9 (11%); Enterococcus, 6 (7%); Gram-negative, 15 (18%); Moraxella, 8 (10%); Pseudomonas, 3 (4%); and Serratia, 3 (4%). Presenting logMAR VA: culture-positive worse than culture-negative cases (2.45 vs 2.19, P = 0.05). Presenting intraocular pressure (IOP): culture-positive higher than culture-negative cases (24 mmHg vs 14 mmHg, P = 0.002). Poor presenting view of the fundus: Streptococcus worse than coagulase-negative Staphylococcus cases (90% vs 44%, P = 0.006), Pseudomonas and Serratia worse than Moraxella cases (100% vs 50%, P = 0.04). Three month logMARΔ: culture-positive worse than culture-negative cases (1.03 vs 0.43, P = 0.02), Streptococcus worse than coagulase-negative Staphylococcus cases (1.44 vs 0.31, P = 0.004), Pseudomonas and Serratia worse than coagulase-negative Staphylococcus cases (2.41 vs 0.31, P = 0.001), Pseudomonas and Serratia worse than Moraxella cases (2.41 vs 0.04, P = 0.001). A culture result of Streptococcus or Serratia was present in 6 of 7 eyes that received an additional treatment of enucleation or evisceration (P = 0.01).Culture-positive cases were associated with worse presenting VA, higher presenting IOP, and worse VA outcomes than culture-negative cases. Streptococcus, Pseudomonas, and Serratia cases were associated with poor presenting view of the fundus and worse VA outcomes than coagulase-negative Staphylococcus and Moraxella cases.

  View details for DOI 10.2147/OPTH.S17975

  View details for PubMedID 21691583

• Endogenous Candida albicans endophthalmitis following spontaneous abortion and IUD removal. Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye Doshi, R. R., Wender, J. D., Jumper, J. M., Sanislo, S. R., Leng, T. 2011; 42 Online: e132-4

  Abstract

  The authors report a rare case of a 32-year-old woman who developed endogenous Candida albicans endophthalmitis following spontaneous abortion and removal of a contraceptive intrauterine device. Considerations regarding diagnosis and management are presented based on a review of the literature.

  View details for DOI 10.3928/15428877-20111208-02

  View details for PubMedID 22165949

• Photodynamic therapy rescue for subretinal fluid exacerbation after focal laser treatment in idiopathic central serous chorioretinopathy. The open ophthalmology journal Leng, T., Sanislo, S. R., Jack, R. L. 2011; 5: 6-9

  Abstract

  To report a case of subretinal leakage after focal laser treatment for idiopathic central serous chorioretinopathy (ICSC). This rare complication was successfully treated with photodynamic therapy (PDT).Interventional case report.A 36-year-old male presented with ICSC in his right eye. After a period of observation without resolution, he was treated with focal laser. That treatment resulted in a massive exacerbation of his subretinal fluid. PDT was successfully used to treat the severe exacerbation with rapid resolution of the subretinal fluid, improvement in visual acuity, decreased leakage on fluorescein angiography, and reduction of subretinal fluid on ophthalmoscopic exam and by optical coherence tomography.Ophthalmologists should consider the use of PDT in cases where focal laser causes an exacerbation of subretinal fluid in ICSC.

  View details for DOI 10.2174/1874364101105010006

  View details for PubMedID 21399767

• Focal periocular carboplatin chemotherapy avoids systemic chemotherapy for unilateral, progressive retinoblastoma. Retina (Philadelphia, Pa.) Leng, T., Cebulla, C. M., Schefler, A. C., Murray, T. G. 2010; 30 (4): S66-8

  Abstract

  The purpose of this study was to report a case of a boy with unilateral, multifocal retinoblastoma who was successfully treated with periocular carboplatin injections for a tumor that progressed despite focal laser ablation.This is an interventional case report. A boy with a paternal history of retinoblastoma and in utero identification of an RB1 mutation was monitored beginning at 2 weeks of age. When the patient was 6 months old, the first tumor was detected and treatment with a direct, ablative, large spot-size diode laser was initiated. During a 38-month period of follow-up, the patient received 23 laser treatments and 3 periocular carboplatin injections (20 mg in 2 mL) to treat 3 tumors in 1 eye.Initially, diode laser ablation of the tumors produced a favorable involutional response of the tumors, associated with a decrease in size and vascularity. Despite aggressive treatment with 12 consecutive laser treatments for 9.7 months, progressive tumor growth was observed in the superonasal tumor, whereas the other 2 tumors remained quiescent. At that time, a series of three focal periocular injections of carboplatin were administered in combination with continued laser ablation. The tumor regressed with type 4 chorioretinal scarring. No systemic chemotherapy or radiation was required.This case of unilateral, multifocal retinoblastoma was successfully treated solely with diode laser ablation and rescue periocular injections of carboplatin after the failure of laser alone. A trial of periocular carboplatin with laser may be considered in cases of unilateral retinoblastoma that are resistant to laser ablation therapy alone.

  View details for PubMedID 20419851

• Intraoperative Use of Three-Dimensional Spectral-Domain Optical Coherence Tomography OPHTHALMIC SURGERY LASERS & IMAGING Ide, T., Wang, J., Tao, A., Leng, T., Kymionis, G. D., O'Brien, T. P., Yoo, S. H. 2010; 41 (2): 250-254

  Abstract

  To develop a prototype three-dimensional anterior segment spectral-domain optical coherence tomography (SD-OCT) device and demonstrate the feasibility of its use in the operating room.Single-institution interventional case series including six consecutive patients undergoing Descemet's stripping automated endothelial keratoplasty (DSAEK). The prototype anterior segment SD-OCT was used intraoperatively to search for the presence of interface fluid between the host cornea and the DSAEK graft.Anterior segment SD-OCT was successfully used intraoperatively during DSAEK. After the initial placement of the graft, no fluid was clinically apparent; however, interface fluid was identified by anterior segment SD-OCT in two of the six cases. After additional aspiration, all patients were fluid-free on follow-up anterior segment SD-OCT scanning.Intraoperative anterior segment SD-OCT was used successfully to find interface fluid that was clinically undetectable under the microscope. As such, all patients were able to leave the operating room with a fully attached graft.

  View details for DOI 10.3928/15428877-20100303-15

  View details for Web of Science ID 000275606400015

  View details for PubMedID 20307045

• Branch retinal artery occlusion after septoplasty. Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye Leng, T., Moshfeghi, D. M. 2010; 41 Online: e1-2

  Abstract

  Loss of vision after uncomplicated rhinosurgery is a rare and uncommon complication. The authors describe a case of branch retinal artery occlusion after septoplasty in a 40-year-old otherwise healthy man. The likely etiology was injection of local anesthetics into the nasal mucosa during surgery. Vision loss could potentially have been prevented through the application of topical vasoconstrictive agents prior to anesthetic injection. Furthermore, slow injection and aspiration prior to injection could also help prevent inadvertent intraarterial injection.

  View details for DOI 10.3928/15428877-20101124-13

  View details for PubMedID 21117572

• Descemet Stripping Automated Endothelial Keratoplasty Tissue Preparation With Femtosecond Laser and Contact Lens CORNEA Ide, T., Yoo, S. H., Kymionis, G. D., Leng, T., Marini, C., Stanciu, N. A., O'Brien, T. P. 2010; 29 (1): 93-98

  Abstract

  To report a novel method of preparing planar Descemet stripping automated endothelial keratoplasty (DSAEK) tissue using a femtosecond laser with a hyperopic soft contact lens (Hyp-SCL).DSAEK tissue was prepared from 11 cadaveric porcine eyes. A femtosecond laser was used to create 400-microm flaps, with or without a Hyp-SCL, after which the eyes were imaged with anterior segment optical coherence tomography. The ratio of the mean central thickness (C) to the mean peripheral thickness (P) was calculated using the flap tool.Eleven eyes were cut (5 without, 5 with, and 1 without and with a Hyp-SCL). In all corneas, the cut interfaces were visualized by anterior segment optical coherence tomography. The mean C:P ratio of the flap made without a Hyp-SCL was 0.998 (range 0.968-1.03, SD = 0.254) compared with 0.904 (range 0.851-0.985, SD = 0.509) with a Hyp-SCL (P = 0.001), demonstrating that a cut made with a Hyp-SCL created a flap that was significantly more concave than that created without a Hyp-SCL, resulting in a more planar DSAEK graft. However, the C:P ratios calculated for DSAEK tissue made without (mean 0.998, range 0.965-1.02, SD = 0.0195) and with (mean 1.02, range 0.986-1.05, SD = 0.0250) a Hyp-SCL did not show significance (P = 0.07).Combining a femtosecond laser and a Hyp-SCL may aid in the creation of planar donor tissue for DSAEK. Clinically, this could reduce the amount of postoperative hyperopic shift, although further human corneal studies are warranted.

  View details for Web of Science ID 000273211500016

  View details for PubMedID 19907309

• Retinal capillary hemangioma in von Hippel-Lindau disease Arch Ophthalmol Leng T, Murray TG 2010; 128 (4): 425
• Branch retinal artery occlusion after septoplasty. Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye Leng, T., Moshfeghi, D. M. 2010; 41 Online: e1-2

  Abstract

  Loss of vision after uncomplicated rhinosurgery is a rare and uncommon complication. The authors describe a case of branch retinal artery occlusion after septoplasty in a 40-year-old otherwise healthy man. The likely etiology was injection of local anesthetics into the nasal mucosa during surgery. Vision loss could potentially have been prevented through the application of topical vasoconstrictive agents prior to anesthetic injection. Furthermore, slow injection and aspiration prior to injection could also help prevent inadvertent intraarterial injection.

  View details for DOI 10.3928/15428877-20101124-13

  View details for PubMedID 22785539

• ENDOPHTHALMITIS CAUSED BY PROTEUS SPECIES Antibiotic Sensitivities and Visual Acuity Outcomes RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., Flynn, H. W., Miller, D., Murray, T. G., Smiddy, W. E. 2009; 29 (7): 1019-1024

  Abstract

  The purpose of this study was to report the clinical presentation, causative organisms, antibiotic sensitivities, management, and visual acuity outcomes in patients with endophthalmitis caused by Proteus species at a university teaching hospital over a 24-year period.This was a retrospective consecutive case series. The Bascom Palmer Eye Institute Microbiology Laboratory database was reviewed to identify all patients with intraocular cultures positive for Proteus species between 1983 and 2007. Clinical records were reviewed to ascertain the clinical presentation, management, and visual acuity outcomes.In the 13 patients identified, all cases followed intraocular surgery, and 1 was associated with a recurrent corneal ulcer. Of the 1,751 organisms isolated from intraocular culture during the study period, 244 were Gram negative. Proteus species represented 5.3% of gram-negative organisms and <1% of the total isolates identified. Endophthalmitis developed 2 days to 14 days postoperatively (median, 3.5 days), and patients were observed 1 month to 61 months after presentation (median, 17 months). Presenting vision ranged from light perception to 20/200. Ten patients had positive cultures for Proteus mirabilis, and three patients had a growth of Proteus morganii. Four patients (31%) were infected with >1 organism. All Proteus isolates were sensitive to the antibiotics clinically administered, including cefazolin, ceftazidime, gentamicin, and the fluoroquinolones. Five patients (38%) initially received intravitreal injections of antibiotics alone, 1 received an anterior chamber washout in combination with intravitreal injections, and 7 patients (54%) received pars plana vitrectomy in combination with intravitreal injections. Two of the patients (15%) who received vitrectomies had either an intraocular lens or retained nuclear fragments removed. Six patients (46%) received additional antibiotic injections during the clinical course, and 6 patients (46%) underwent additional surgical procedures. Final visual acuity was better than light perception in 5 patients (38%) and was light perception or no light perception in 8 patients (62%). Only 4 patients (31%) had a final vision acuity > or =5/200.Despite prompt treatment with appropriate antibiotics, the clinical outcome for Proteus species endophthalmitis is often poor.

  View details for Web of Science ID 000267955400017

  View details for PubMedID 19584659

• SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS OF CUTICULAR DRUSEN RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., Rosenfeld, P. J., Gregori, G., Puliafito, C. A., Punjabi, O. S. 2009; 29 (7): 988-993

  Abstract

  To evaluate the appearance of cuticular drusen with spectral domain optical coherence tomography.Eyes of patients with cuticular drusen were imaged using a prototype spectral domain optical coherence tomography instrument with 5-microm axial resolution. Thickness maps were obtained after automated segmentation of the internal limiting membrane and retinal pigment epithelium layers using a proprietary algorithm. The volume of subretinal fluid (SRF) was calculated using a manual segmentation technique that involved drawing boundaries around the SRF. The repeatability of these measurements was tested by comparing the volume measurements from multiple scans performed on the same day in four eyes of three patients.Sixteen eyes from eight patients with cuticular drusen were scanned. Areas of decreased retinal thickness overlying drusen were best visualized using the three-dimensional retinal thickness map. The distribution and sawtooth pattern of cuticular drusen were best visualized using three-dimensional retinal pigment epithelium segmentation. Of the 16 eyes, 13 had SRF within the macula. In the eyes with macular SRF, characteristic excrescences were present along the outer retina and attenuation of the photoreceptor inner and outer segment boundary were observed in many areas. In areas where the retina was detached, the retinal pigment epithelium-Bruch's membrane complex appeared nodular or attenuated. The volumetric measurements of the SRF were performed using a manual segmentation with a 1.11% mean difference between repeated measurements on the same day (range, 0.47-1.68%; standard deviation, 0.55%).The sawtooth pattern of drusen and the presence of excrescences along the detached outer retina are characteristic features of cuticular drusen that should be helpful in confirming the diagnosis of this condition. The volumetric analysis of the SRF is repeatable and may be useful in following the clinical course of these patients.

  View details for Web of Science ID 000267955400013

  View details for PubMedID 19584657

• Retinal Vascular Tumor and Peripheral Retinal Vasculitis in the Setting of Systemic Tuberculosis OPHTHALMIC SURGERY LASERS & IMAGING Leng, T., Schefler, A. C., Murray, T. G. 2009; 40 (4): 409-412

  Abstract

  Tuberculosis commonly affects the eye by causing neovascularization, peripheral vasculitis, and choroidal tubercles. The authors describe a 28-year-old man with systemic tuberculosis who presented with a retinal vascular tumor, peripheral retinal vasculitis, retinal neovascularization, and vitreous hemorrhage causing acute vision loss. He was successfully treated with systemic anti-tuberculosis medications, retinal photocoagulation, and focal ablative diode laser to the tumor. Ophthalmologists should consider performing a purified protein derivative test and a chest x-ray for any patient with a history suspicious for tuberculosis who presents with a vascular tumor.

  View details for DOI 10.3928/15428877-20096030-11

  View details for Web of Science ID 000268127800011

  View details for PubMedID 19634748

• Eyelid and orbital implant injury after enucleation OphthalmologyWeb Leng T 2009
• Subconjunctival Air Leakage After Descemet's Stripping Automated Endothelial Keratoplasty(DSAEK) in a Post-Trabeculectomy Eye. The open ophthalmology journal Ide, T., Yoo, S. H., Leng, T., O'Brien, T. P. 2009; 3: 1-2

  Abstract

  To report a case of subconjunctival air leakage from the anterior chamber (AC) into a trabeculectomy bleb after Descemet's stripping automated endothelial keratoplasty (DSAEK).An 89 year-old woman with a previous history of primary open angle glaucoma in her left eye and previous trabeculectomy with mitomycin C had DSAEK on the patient's left eye in order to treat her endothelial disease. During the DSAEK procedure, air was injected into the AC to aid in graft adherence.The day after the surgery, subconjunctival air leakage from the AC into a trabeculectomy bleb was observed.Although our patient did not have any complications from this leak, there exists the potential for hypotony, bleb-related infections, and dislocations of the DSAEK graft. Given the potential consequences, these patients should be monitored closely.

  View details for DOI 10.2174/1874364100903010001

  View details for PubMedID 19554220

• Three-dimensional spectral domain optical coherence tomography of a clear corneal cataract incision OPHTHALMIC SURGERY LASERS & IMAGING Leng, T., Lujan, B. J., Yoo, S. H., Wang, J. 2008; 39 (4): S132-S134

  Abstract

  A prototype 1,310-nm wavelength spectral domain optical coherence tomography (SD-OCT) instrument was constructed and mounted onto a conventional slit lamp for imaging of the anterior segment. The device had an axial resolution of 8 microm and was able to acquire real-time two-dimensional images at 14 frames/second and full three-dimensional datasets in approximately 7 seconds. An SD-OCT dataset of 100 B-scans, each consisting of 512 A-scans, was acquired from the left eye ofa patient who had undergone phacoemulsification with a clear corneal incision. The resulting dataset could be manipulated in three-dimensional space to analyze the geometry of the wound. Additionally, stromal edema and iris features were clearly imaged with the device. SD-OCT can be used to analyze clear corneal incisions to determine optimal wound construction technique and geometry as they relate to the prevention of complications such as postoperative wound leak, infection, and epithelial ingrowth.

  View details for Web of Science ID 000258283000025

  View details for PubMedID 18777882

• Glaucoma valves and shunts OphthalmologyWeb Leng T 2008
• A model retinal interface based on directed neuronal growth for single cell stimulation BIOMEDICAL MICRODEVICES Mehenti, N. Z., Tsien, G. S., Leng, T., Fishman, H. A., Bent, S. F. 2006; 8 (2): 141-150

  Abstract

  In this work, we use cell micropatterning technologies to direct neuronal growth to individual electrodes, and demonstrate that such an approach can achieve selective stimulation and lower stimulation thresholds than current field-effect based retinal prostheses. Rat retinal ganglion cells (RGCs) were purified through immunopanning techniques, and microcontact printing (microCP) was applied to align and pattern laminin on a microelectrode array, on which the RGCs were seeded and extended neurites along the pattern to individual electrodes. The stimulation threshold currents of RGCs micropatterned to electrodes were found to be significantly less than those of non-patterned RGCs over a wide range of electrode-soma distances, as determined with calcium imaging techniques. Moreover, the stimulation threshold for micropatterned cells was found to be independent of electrode-soma distance, and there was no significant effect of microCP on cell excitability. The effects of additional stimulation parameters, such as electrode size and pulse duration, on threshold currents were determined. The stimulation results quantitatively demonstrate the potential benefits of a retinal prosthetic interface based on directed neuronal growth.

  View details for DOI 10.1007/s10544-006-7709-3

  View details for Web of Science ID 000237486500006

  View details for PubMedID 16688573

• Full thickness retinal pigment epithelium explants proliferate into epithelial monolayers on synthetic Bruch's membrane substitutes Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Lombardi, L., Leng, T., Yeh, E., Molnar, F., Noolandi, J., Marmor, M. F., Fishman, H. A., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2005

  View details for Web of Science ID 000227980404442

• Synthetic Bruch's membrane substitutes: Comparisons after subretinal transplantation with cultured iris pigment epithelium Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Molnar, F. E., Lombardi, L., Berker, N., Yeh, E., Yellachich, D., Leng, T., Dalal, R., Marmor, M. F., Fishman, H. A., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2005

  View details for Web of Science ID 000227980404446

• Directed retinal nerve cell growth for use in a retinal prosthesis interface INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Leng, T., Wu, P., Mehenti, N. Z., Bent, S. F., Marmor, M. F., Blumenkranz, M. S., Fishman, H. A. 2004; 45 (11): 4132-4137

  Abstract

  Retinal prosthetic devices that use microelectrode arrays to stimulate retinal nerve cells may provide a viable treatment for degenerative retinal diseases. Current devices are based on electrical field-effect stimulation of remaining functional neural elements. However, the distance between target neurons and electrodes limits the potential density of electrodes and the ability to stimulate specific types of retinal neurons that contribute to visual perceptions. This study was conducted to investigate the use of microcontact printing (muCP) to direct cultured or explant retinal ganglion cell (RGC) neurites to precise and close stimulation positions and to evaluate the cell types that grow from a retinal explant.RGCs and whole retinal explants were isolated from postnatal day-7 Sprague-Dawley rats using immunopanning purification and microdissection, respectively. Aligned muCP was used to direct the growth of RGC neurites from pure cultures (n=105) and retinal explants (n=64) along laminin patterns and to individual microelectrodes. Immunofluorescence stains (n=39) were used to determine the cell types that grew out from the retinal explants.RGC neurite growth was directed reproducibly along aligned laminin micropatterns to individual microelectrodes in pure RGC cultures and from full-thickness explanted rat retinas in 92% of experiments, neurites from pure RGC cultures extended along the laminin lines with an average length of 263 +/- 118 microm (SD; n=27) after 24 hours. Neurites from retinal explants extended in more than 80% of experiments and were observed to grow to an average length of 279 +/- 78 microm (n=64) after 2 days in culture. These neurites grew up to 3 mm after 1 month of culture on the laminin micropatterns. Immunohistochemical stains demonstrated that extended processes from both RGCs and glial cells grew out of retinal explants onto stamped laminin lines.Using muCP to pattern surfaces with growth factors, individual neuronal processes from pure RGC culture and whole retinal explants can be directed to discrete sites on a microelectronic chip surface. By directing RGC neurite processes to specific sites, single cell stimulation becomes possible. This may allow discrete populations of retinal neurons to be addressed so that physiologic retinal processing of visual information can be achieved.

  View details for DOI 10.1167/iovs.03-1335

  View details for PubMedID 15505066

• The chick chorioallantoic membrane as a model tissue for surgical retinal research and simulation RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., MILLER, J. M., Bilbao, K. V., Palanker, D. V., Huie, P., Blumenkranz, M. S. 2004; 24 (3): 427-434

  Abstract

  We describe the use of chick chorioallantoic membrane (CAM) as a model system for the study of the precision and safety of vitreoretinal microsurgical instruments and techniques.The CAM was prepared for experimentation with and without its inner shell membrane (ISM) attached for in vivo and in vitro experiments that simulated medical and surgical interventions on the retina.The CAM's ease of use, low cost, and anatomic structure make it a convenient model for surgical retinal and retinal vascular modeling.While CAM has been used extensively in the past for ocular angiogenesis studies, we describe the tissue as a useful tool for a variety of other applications, including (1) testing of novel surgical tools and techniques for cutting and coagulating retina and its vasculature, (2) testing vessel cannulation and injection techniques, (3) angiographic studies, and (4) endoscopic surgery.

  View details for Web of Science ID 000222156800014

  View details for PubMedID 15187666

• Fabrication and characterization of a carbon nanotube microelectrode array for retinal prostheses Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Wang, K., Dai, H., Leng, T., Mehenti, N. Z., Harris, J. S., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2004: U379–U379

  View details for Web of Science ID 000223338201366

• Retinal light processing using carbon nanotubes Official Gazette of the USPTO Patents Loftus D, Leng T, Fishman HA 2004; 1283 (5)
• The artificial synapse chip: A flexible retinal interface based on directed retinal cell growth and neurotransmitter stimulation ARTIFICIAL ORGANS Peterman, M. C., Mehenti, N. Z., Bilbao, K. V., Lee, C. J., Leng, T., Noolandi, J., Bent, S. F., Blumenkranz, M. S., Fishman, H. A. 2003; 27 (11): 975-985

  Abstract

  The Artificial Synapse Chip is an evolving design for a flexible retinal interface that aims to improve visual resolution of an electronic retinal prosthesis by addressing cells individually and mimicking the physiological stimulation achieved in synaptic transmission. We describe three novel approaches employed in the development of the Artificial Synapse Chip: (i) micropatterned substrates to direct retinal cell neurite growth to individual stimulation sites; (ii) a prototype retinal interface based on localized neurotransmitter delivery; and (iii) the use of soft materials to fabricate these devices. By patterning the growth of cells to individual stimulation sites, we can improve the selectivity of stimulation and decrease the associated power requirements. Moreover, we have microfabricated a neurotransmitter delivery system based on a 5- micro m aperture in a 500-nm-thick silicon nitride membrane overlying a microfluidic channel. This device can release neurotransmitter volumes as small as 2 pL, demonstrating the possibility of chemical-based prostheses. Finally, we have fabricated and implanted an equivalent device using soft flexible materials that conform to the retinal tissue more effectively. As many of the current retinal prosthesis devices use hard materials and electrical excitation at a lower resolution, our approach may provide more physiologic retinal stimulation.

  View details for Web of Science ID 000186491900003

  View details for PubMedID 14616516

• Wiggling subcutaneous lumps. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Leng, T., Smith, D. S. 2003; 37 (4): 542, 591-2

  View details for DOI 10.1086/377179

  View details for PubMedID 12905150

• Wiggling subcutaneous lumps - Furuncular myiasis due to Dermatobia hominis larvae CLINICAL INFECTIOUS DISEASES Leng, T., Smith, D. S. 2003; 37 (4): 542-?

  View details for Web of Science ID 000184618900011

• Cell demographics from full thickness retinal explant growth on micropatterned surfaces Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Wu, P., Mehenti, N. Z., Leng, T., Marmor, M. F., Blumenkranz, M. S., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2003: U692–U692

  View details for Web of Science ID 000184607002467

• A retinal interface based on neurite micropatterning for single cell stimulation Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Mehenti, N. Z., Peterman, M. C., Leng, T., Marmor, M. F., Blumenkranz, M. S., Bent, S. F. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2003: U704–U704

  View details for Web of Science ID 000184607002529

• Microcontact printing on human tissue for retinal cell transplantation ARCHIVES OF OPHTHALMOLOGY Lee, C. J., Huie, P., Leng, T., Peterman, M. C., Marmor, M. F., Blumenkranz, M. S., Bent, S. F., Fishman, H. A. 2002; 120 (12): 1714-1718

  Abstract

  To demonstrate that microcontact printing, a modern materials fabrication technique, can be used to engineer the surface of human tissue and to show that inhibitory molecules can be used to pattern the growth of retinal pigment epithelial cells or iris pigment epithelial cells on human lens capsule for transplantation.Photolithographic techniques were used to fabricate photoresist-coated silicon substrates into molds. Poly(dimethylsiloxane)stamps for microcontact printing were made from these molds. The poly(dimethylsiloxane) stamps were then used to "wet-transfer" growth inhibitory molecules to the surface of prepared human lens capsules that were obtained during cataract surgery. Human retinal pigment epithelial and rabbit iris pigment epithelial cells were grown on a lens capsule substrate in the presence and absence of a patterned array of inhibitory factors.We found that human lens capsule could be microprinted with a precision similar to that obtained on glass or synthetic polymers. Retinal pigment epithelial cells and iris pigment epithelial cells cultured onto an untreated lens capsule showed spreading and formed into fusiform-appearing cells. In contrast, cells cultured on a lens capsule with a hexagonal micropattern of growth inhibitory molecules retained an epithelioid form within the inhibitory hexagons.Inhibitory growth molecules can be micropatterned onto human lens capsule, and these micropatterns can control the organization of retinal pigment epithelial cells or iris pigment epithelial cells cultured onto the lens capsule surface.Microprinting on autologous human tissue may facilitate efforts to effectively organize cell cultures and transplantations for the replacement of vital ocular tissues such as the retinal pigment epithelium in age-related macular degeneration.

  View details for PubMedID 12470147

• A biodegradable matrix facilitates the use of lens capsule as a substrate for subretinal cell transplantation Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Bilbao, K. V., Leng, T., Fung, A. E., Huie, P., Sanislo, S. R., Marmor, M. F., Blumenkranz, M. S., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U972–U972

  View details for Web of Science ID 000184606700593

• Tissue engineered lens capsule as a substrate for IPE and RPE transplantation Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Fung, A. E., Lee, C. J., Leng, T., Bilbao, L. V., Peterman, M. C., Blumenkranz, M. S., Bent, S. F., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U973–U973

  View details for Web of Science ID 000184606700604

• The artificial synapse chip: A novel interface for a retinal prosthesis based on neurotransmitter stimulation and nerve regeneration Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Fishman, H. A., Peterman, M. C., Leng, T., Huie, P., Lee, C. J., Bloom, D. M., Sanislo, S. R., Marmor, M. F., Bent, S. F., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U803–U803

  View details for Web of Science ID 000184606700013

• Directed ganglion cell growth and stimulation with microcontact printing as a prototype visual prosthesis interface Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Leng, T., Huie, P., Mehenti, N. Z., Peterman, M. C., Lee, C. J., Marmor, M. F., Sanislo, S. R., Beni, S. F., Blumenkranz, M. S., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U1279–U1279

  View details for Web of Science ID 000184606701608

• Novel interface to biological systems for retinal prosthetics Symposium on MEMS and BioMEMS held at the 2002 MRS Spring Meeting Peterman, M. C., Lee, C., Leng, T., Huie, P., Fishman, H. A. MATERIALS RESEARCH SOCIETY. 2002: 149–154

  View details for Web of Science ID 000178928100021

• A real world lesson The Bulletin of the Santa Clara County Medical Association Leng T 2001; 7 (6): 6-7
• Capillary electrophoresis coupled with RBL-2H3 cells as a single-cell biosensor Stanford University Department of Biological Sciences Honors Thesis Leng T, Zare RN 1999